MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Free Radical Biology and Medicine' source. Thu, 09 Feb 2012 14:32:08 +0100 http://www.medworm.com/index.php?rid=5656229&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22285390%26dopt%3DAbstract This study was designed to investigate the effects of geranylgeranylacetone (GGA), a pharmacological inducer of Trx-1 and Hsp70, on morphine-induced hyperlocomotion, rewarding effect, and withdrawal syndrome. Trx-1 and Hsp70 expression was increased in the frontal cortex, hippocampus, ventral tegmental area, and nucleus accumbens of mice after GGA treatment. GGA administration reduced morphine-induced motor activity and inhibited conditioned place preference. GGA markedly attenuated the morphine-naloxone-induced withdrawal signs, including jumping, rearing, and forepaw tremor. Furthermore, the activation of cAMP-responsive element-binding protein and the expression of ΔFosB and cyclin-dependent kinase 5 were decreased in the nucleus accumbens by GGA treatment after morphine withdrawal. In... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5656229 Wed, 18 Jan 2012 05:00:00 +0100 5656229 http://www.medworm.com/index.php?rid=5656228&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22285391%26dopt%3DAbstract In this study, we examined the physiological role of mPTP opening in renal calcium crystallization in vitro and in vivo. In the in vitro study, cultured renal tubular cells were exposed to calcium oxalate monohydrate (COM) crystals and treated with CsA (2μM). COM crystals induced depolarization of the mitochondrial membrane potential and generated oxidative stress as evaluated by Cu-Zn SOD and 4-HNE. Furthermore, the expression of cytochrome c and cleaved caspase 3 was increased and these effects were prevented by CsA. In the in vivo study, Sprague-Dawley rats were administered 1% ethylene glycol (EG) to generate a rat kidney stone model and then treated with CsA (2.5, 5.0, and 10.0mg/kg/day) for 14days. EG administration induced renal calcium crystallization, which was prevented by CsA. ... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5656228 Wed, 18 Jan 2012 05:00:00 +0100 5656228 http://www.medworm.com/index.php?rid=5636990&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22281400%26dopt%3DAbstract Authors: Smith JK, Patil CN, Patlolla S, Gunter BW, Booz GW, Duhé RJ Abstract Four cysteine residues (Cys866, Cys917, Cys1094, and Cys1105) have direct roles in cooperatively regulating Janus kinase 2 (JAK2) catalytic activity. Additional site-directed mutagenesis experiments now provide evidence that two of these residues (Cys866 and Cys917) act together as a redox-sensitive switch, allowing JAK2's catalytic activity to be directly regulated by the redox state of the cell. We created several variants of the truncated JAK2 (GST/(NΔ661)rJAK2), which incorporated cysteine-to-serine or cysteine-to-alanine mutations. The catalytic activities of these mutant enzymes were evaluated by in vitro autokinase assays and by in situ autophosphorylation and transphosphorylation assays. Cystein... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5636990 Sun, 15 Jan 2012 05:00:00 +0100 5636990 http://www.medworm.com/index.php?rid=5636991&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22281399%26dopt%3DAbstract Authors: Bretón-Romero R, de Orduña CG, Romero N, Sánchez FJ, de Álvaro C, Porras A, Rodríguez-Pascual F, Laranjinha J, Radi R, Lamas S Abstract Laminar shear stress (LSS) is a protective hemodynamic regulator of endothelial function and limits the development of atherosclerosis and other vascular wall diseases related to pathophysiological generation of reactive oxygen species. LSS activates several endothelial signaling responses, including the activation of MAPKs and eNOS. Here, we explored the mechanisms of activation of these key endothelial signaling pathways. Using the cone/plate model we found that LSS (12dyn/cm(2)) rapidly (5-60min) promotes endothelial intracellular generation of superoxide and hydrogen peroxide (H(2)O(2)). Physiological concentrations of H(2)O(2) (f... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5636991 Sat, 14 Jan 2012 05:00:00 +0100 5636991 http://www.medworm.com/index.php?rid=5636993&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22266045%26dopt%3DAbstract Authors: Gould NS, Min E, Martin RJ, Day BJ Abstract One of the most abundant antioxidants in the lung is glutathione (GSH), a low-molecular-weight thiol, which functions to attenuate both oxidative stress and inflammation. GSH is concentrated in the epithelial lining fluid (ELF) of the lung and can be elevated in response to the increased oxidant burden from cigarette smoke (CS). However, the transporter(s) responsible for the increase in ELF GSH with cigarette smoke is not known. Three candidate apical GSH transporters in the lung are CFTR, BCRP, and MRP2, but their potential roles in ELF GSH transport in response to CS have not been investigated. In vitro, the inhibition of CFTR, BCRP, or MRP2 resulted in decreased GSH efflux in response to cigarette smoke extract. In vivo, mice... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5636993 Thu, 12 Jan 2012 05:00:00 +0100 5636993 http://www.medworm.com/index.php?rid=5636992&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22269608%26dopt%3DAbstract In this study, we examined how modifications in cAMP signaling affected the production of hydroxyl radicals in rat striatum using microdialysis to measure extracellular 2,3-dihydroxybenzoic acid (2,3-DHBA), which is a hydroxyl radical adduct of salicylate. Up to 50nmol of the cell-permeative cAMP mimetic 8-bromo-cAMP (8-Br-cAMP) increased 2,3-DHBA in a dose-dependent manner (there was no additional increase in 2,3-DHBA at 100nmol). Another cAMP mimetic, dibutyryl cAMP (db-cAMP), caused a nonsignificant increase in 2,3-DHBA at 50nmol and a significant decrease at 100nmol. Up to 20nmol of forskolin, which is a direct activator of adenylyl cyclase, increased 2,3-DHBA, similar to the effect of 8-Br-cAMP; however, forskolin resulted in a much greater increase in 2,3-DHBA. A potent inhibitor of ... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5636992 Thu, 12 Jan 2012 05:00:00 +0100 5636992 http://www.medworm.com/index.php?rid=5636994&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22265930%26dopt%3DAbstract Authors: Yadav SK, Adhikary B, Chand S, Maity B, Bandyopadhyay SK, Chattopadhyay S Abstract The probable cross talk among large numbers of inflammatory and angiogenic parameters in indomethacin (IND)-induced gastropathy and the associated signaling mechanism were studied in a mouse model. A single dose of IND (18mg/kg, po) produced robust gastric ulceration in mice without any mortality, which peaked on the third day, but started healing from the fifth day onward. The ulceration was associated with increased myeloperoxidase activity and expression of proinflammatory (TNF-α, adhesion molecules, COX-2) and antiangiogenic (endostatin) parameters. The levels of proangiogenic factors such as COX-1, prostaglandin E, VEGF, and von Willebrand factor VIII were downregulated by IND. Our res... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5636994 Wed, 11 Jan 2012 05:00:00 +0100 5636994 http://www.medworm.com/index.php?rid=5619199&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248862%26dopt%3DAbstract Authors: Barrett TJ, Pattison DI, Leonard SE, Carroll KS, Davies MJ, Hawkins CL Abstract Myeloperoxidase (MPO) forms reactive oxidants including hypochlorous and hypothiocyanous acids (HOCl and HOSCN) under inflammatory conditions. HOCl causes extensive tissue damage and plays a role in the progression of many inflammatory-based diseases. Although HOSCN is a major MPO oxidant, particularly in smokers, who have elevated plasma thiocyanate, the role of this oxidant in disease is poorly characterized. HOSCN induces cellular damage by targeting thiols. However, the specific targets and mechanisms involved in this process are not well defined. We show that exposure of macrophages to HOSCN results in the inactivation of intracellular enzymes, including creatine kinase (CK) and glyceralde... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5619199 Sun, 08 Jan 2012 05:00:00 +0100 5619199 http://www.medworm.com/index.php?rid=5619201&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245096%26dopt%3DAbstract Authors: Grimm S, Horlacher M, Catalgol B, Hoehn A, Reinheckel T, Grune T Abstract Advanced glycation end product-modified proteins are known for accumulating during aging and in several pathological conditions such as diabetes, renal failure, and neurodegenerative disorders. There is little information about the intracellular fate of endocytosed advanced glycation end products (AGEs) and their influence on proteolytic systems. However, it is known that the lysosomal system is impaired during aging. Therefore, undegraded material may accumulate and play a considerable role in the development of diverse diseases. To investigate if AGEs can be degraded and to test whether they accumulate because of impaired lysosomal proteases we studied the effects of advanced glycation end products... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5619201 Wed, 04 Jan 2012 05:00:00 +0100 5619201 http://www.medworm.com/index.php?rid=5619200&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245097%26dopt%3DAbstract Authors: Li Q, Tomcik K, Zhang S, Puchowicz MA, Zhang GF Abstract Our previous work in perfused rat livers has demonstrated that 4-hydroxynonenal (HNE) is catabolized predominantly via β oxidation. Therefore, we hypothesized that perturbations in β oxidation, such as diet-altered fatty acid oxidation activity, could lead to changes in HNE levels. To test our hypothesis, we (i) developed a simple and sensitive GC/MS method combined with mass isotopomer analysis to measure HNE and HNE analogs, 4-oxononenal (ONE) and 1,4-dihydroxynonene (DHN), and (ii) investigated the effects of four diets (standard, low-fat, ketogenic, and high-fat mix) on HNE, ONE, and DHN concentrations in rat livers. Our results showed that livers from rats fed the ketogenic diet or high-fat mix diet had high �... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5619200 Wed, 04 Jan 2012 05:00:00 +0100 5619200 http://www.medworm.com/index.php?rid=5619203&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245094%26dopt%3DAbstract We report that the exposure of normal human keratinocytes (NHKs) or melanocytes (NHEMs) to mild hypoxia drastically impacts cell death responses following UVB irradiation. The hypoxic microenvironment favors survival and reduces apoptosis of UVB-irradiated NHEMs and their malignant counterparts (melanoma cells). In contrast, NHKs, but not the transformed keratinocytes, under hypoxic conditions display increased levels of reactive oxygen species (ROS) and are significantly sensitized to UVB-mediated apoptosis as compared to NHKs treated under normoxic conditions. Prolonged exposure of UVB-treated NHKs to hypoxia triggers a sustained and reactive oxygen species-dependent activation of the stress kinases p38(MAPK) and JNKs, which in turn, engage the activation of Noxa and Bim proapoptotic pro... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5619203 Mon, 02 Jan 2012 05:00:00 +0100 5619203 http://www.medworm.com/index.php?rid=5619202&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245095%26dopt%3DAbstract In conclusion, this study suggests that GRP94 overexpression may be a hallmark of aggressiveness and recurrence in breast cancers. PMID: 22245095 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine) Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5619202 Mon, 02 Jan 2012 05:00:00 +0100 5619202 http://www.medworm.com/index.php?rid=5595453&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22240154%26dopt%3DAbstract This study identifies a link between oxidative stress, TGF-β1 and EMT in lung epithelium and highlights the potential for antioxidant therapies to limit EMT and its potential contribution to chronic lung disease. PMID: 22240154 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine) Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5595453 Mon, 02 Jan 2012 05:00:00 +0100 5595453 http://www.medworm.com/index.php?rid=5595452&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22240155%26dopt%3DAbstract In this study we investigated the effect of Hg(II) (HgCl(2)) on GJIC in cultured human keratinocytes. It is shown that subcytotoxic concentrations of HgCl(2) as low as 10 nM cause inhibition of the GJIC, assessed by dye transfer assay, despite enhanced expression of connexins. In addition, HgCl(2)-treated keratinocytes exhibited a decrease of free thiols and accumulation of mitochondria-derived reactive oxygen species, albeit no effect on the respiratory chain activity was observed. Treatment of HgCl(2)-exposed keratinocytes with the PKC inhibitor calphostin C and with all-trans retinoic acid resulted in rescue of the mitochondrial ROS overproduction and full recovery of the GJIC. Similar results were obtained with the PKA activator db-cAMP. Overall, the presented results support a cross-t... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5595452 Mon, 02 Jan 2012 05:00:00 +0100 5595452 http://www.medworm.com/index.php?rid=5595454&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22240153%26dopt%3DAbstract Authors: Mora-Pale M, Joon-Kwon S, Linhardt RJ, Dordick JS Abstract Enzymatically derived oligophenols from apocynin can be effective inhibitors of human vascular NADPH oxidase (Nox). An isolated trimer hydroxylated quinone (IIIHyQ) has been shown to inhibit endothelial NADPH oxidase with an IC(50) ~30 nM. In vitro studies demonstrated that IIIHyQ is capable of disrupting the interaction between p47(phox) and p22(phox), thereby blocking the activation of the Nox2 isoform. Herein, we report the role of key cysteine residues in p47(phox) as targets for the IIIHyQ. Incubation of p47(phox) with IIIHyQ results in a decrease of ~80% of the protein free cysteine residues; similar results were observed using 1,2- and 1,4-naphthoquinones, whereas apocynin was unreactive. Mutants of p47(phox... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5595454 Thu, 29 Dec 2011 05:00:00 +0100 5595454 http://www.medworm.com/index.php?rid=5595456&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22240151%26dopt%3DAbstract Authors: Liu Y, Tang L, Chen B Abstract Retinal ischemia/reperfusion (I/R) results in neuronal death and generation of reactive oxygen species. The aim of this study was to investigate the neuroprotective effect of manganese superoxide dismutase (SOD2) on retinal ganglion cells (RGCs) in an I/R-induced retinal injury model. One eye of each Wistar rat was pretreated with recombinant adeno-associated virus containing the SOD2 gene (AAV-SOD2) or recombinant AAV containing the GFP gene (AAV-GFP) by intravitreal injection 21days before initiation of I/R injury. Retinal I/R injury was induced by elevating intraocular pressure for 1h, and reperfusion was established immediately afterward. The number of RGCs and the inner plexiform layer (IPL) thickness were measured by Fluorogold retrogra... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5595456 Sat, 24 Dec 2011 05:00:00 +0100 5595456 http://www.medworm.com/index.php?rid=5595458&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22226831%26dopt%3DAbstract Authors: Back P, De Vos WH, Depuydt GG, Matthijssens F, Vanfleteren JR, Braeckman BP Abstract Reactive oxygen species (ROS) are no longer considered merely toxic by-products of the oxidative metabolism. Tightly controlled concentrations of ROS and fluctuations in redox potential may be important mediators of signaling processes. Understanding the role of ROS and redox status in physiology, stress response, development, and aging requires their nondisruptive, spatiotemporal, real-time quantification in a living organism. We established Caenorhabditis elegans strains bearing the genetically encoded fluorescent biosensors HyPer and Grx1-roGFP2 for the detection of hydrogen peroxide (H(2)O(2)) and the glutathione redox potential, respectively. Although, given its transparency and genet... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5595458 Fri, 23 Dec 2011 05:00:00 +0100 5595458 http://www.medworm.com/index.php?rid=5595457&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22240150%26dopt%3DAbstract Authors: Leung CK, Empinado H, Choe KP Abstract The nucleolus has recently emerged as a major coordinator of cellular stress responses by regulating the tumor suppressor p53. However, it is not known if the nucleolus regulates the cap 'n' collar (CnC) transcription factors SKN-1 and Nrf2, which activate conserved antioxidant and detoxification responses in C. elegans and mammals, respectively. A screen for negative regulators of detoxification genes in C. elegans identified the conserved WD40 repeat containing protein WDR-46. This protein is highly conserved with yeast UTP7, which functions in 18S rRNA processing and assembly of the 40S small ribosomal subunit. WDR-46 is expressed in the nucleoli of multiple tissues in C. elegans and is required for rRNA processing. Mutation or sil... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5595457 Fri, 23 Dec 2011 05:00:00 +0100 5595457 http://www.medworm.com/index.php?rid=5595455&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22240152%26dopt%3DAbstract In this study, we developed a method for the analysis of structurally related flavanol metabolites using a wide range of authentic standards. Applying this method in the context of a human dietary intervention study using comprehensively characterized and standardized flavanol- and procyanidin-containing cocoa, we were able to identify the structurally related (-)-epicatechin metabolites (SREM) postprandially extant in the systemic circulation of humans. Our results demonstrate that (-)-epicatechin-3'-β-d-glucuronide, (-)-epicatechin-3'-sulfate, and a 3'-O-methyl-(-)-epicatechin-5/7-sulfate are the predominant SREM in humans and further confirm the relevance of the stereochemical configuration in the context of flavanol metabolism. In addition, we also identified plausible causes for the ... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5595455 Fri, 23 Dec 2011 05:00:00 +0100 5595455 http://www.medworm.com/index.php?rid=5576764&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210378%26dopt%3DAbstract Authors: Gaete PS, Lillo MA, Ardiles NM, Pérez FR, Figueroa XF Abstract Ca(2+)-activated K(+) channels (K(Ca)) and NO play a central role in the endothelium-dependent control of vasomotor tone. We evaluated the interaction of K(Ca) with NO production in isolated arterial mesenteric beds of the rat. In phenylephrine-contracted mesenteries, acetylcholine (ACh)-induced vasodilation was reduced by NO synthase (NOS) inhibition with N(ω)-nitro-l-arginine (L-NA), but in the presence of tetraethylammonium, L-NA did not further affect the response. In KCl-contracted mesenteries, the relaxation elicited by 100nM ACh or 1μM ionomycin was abolished by L-NA, tetraethylammonium, or simultaneous blockade of small-conductance K(Ca) (SK(Ca)) channels with apamin and intermediate-conductance K(Ca... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5576764 Fri, 23 Dec 2011 05:00:00 +0100 5576764 http://www.medworm.com/index.php?rid=5576762&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22214747%26dopt%3DAbstract Authors: Cook NL, Viola HM, Sharov VS, Hool LC, Schöneich C, Davies MJ Abstract The sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) plays a critical role in Ca(2+) homeostasis via sequestration of this ion in the sarco/endoplasmic reticulum. The activity of this pump is inhibited by oxidants and impaired in aging tissues and cardiovascular disease. We have shown previously that the myeloperoxidase (MPO)-derived oxidants HOCl and HOSCN target thiols and mediate cellular dysfunction. As SERCA contains Cys residues critical to ATPase activity, we hypothesized that HOCl and HOSCN might inhibit SERCA activity, via thiol oxidation, and increase cytosolic Ca(2+) levels in human coronary artery endothelial cells (HCAEC). Exposure of sarcoplasmic reticulum vesicles to preformed or enzyma... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5576762 Fri, 23 Dec 2011 05:00:00 +0100 5576762 http://www.medworm.com/index.php?rid=5576769&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22203369%26dopt%3DAbstract Authors: Midwinter RG, Maghzal GJ, Dennis JM, Wu BJ, Cai H, Kapralov AA, Belikova NA, Tyurina YY, Dong LF, Khachigian L, Neuzil J, Kagan VE, Stocker R Abstract Probucol inhibits the proliferation of vascular smooth muscle cells in vitro and in vivo, and the drug reduces intimal hyperplasia and atherosclerosis in animals via induction of heme oxygenase-1 (HO-1). Because the succinyl ester of probucol, succinobucol, recently failed as an antiatherogenic drug in humans, we investigated its effects on smooth muscle cell proliferation. Succinobucol and probucol induced HO-1 and decreased cell proliferation in rat aortic smooth muscle cells. However, whereas inhibition of HO-1 reversed the antiproliferative effects of probucol, this was not observed with succinobucol. Instead, succinobuc... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5576769 Wed, 21 Dec 2011 05:00:00 +0100 5576769 http://www.medworm.com/index.php?rid=5576768&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206977%26dopt%3DAbstract Authors: Muzio G, Maggiora M, Paiuzzi E, Oraldi M, Canuto RA Abstract Aldehyde dehydrogenases (ALDHs) oxidize aldehydes to the corresponding carboxylic acids using either NAD or NADP as a coenzyme. Aldehydes are highly reactive aliphatic or aromatic molecules that play an important role in numerous physiological, pathological, and pharmacological processes. ALDHs have been discovered in practically all organisms and there are multiple isoforms, with multiple subcellular localizations. More than 160 ALDH cDNAs or genes have been isolated and sequenced to date from various sources, including bacteria, yeast, fungi, plants, and animals. The eukaryote ALDH genes can be subdivided into several families; the human genome contains 19 known ALDH genes, as well as many pseudogenes. Notewort... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5576768 Wed, 21 Dec 2011 05:00:00 +0100 5576768 http://www.medworm.com/index.php?rid=5576767&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206978%26dopt%3DAbstract Authors: Brimfield AA, Soni SD, Trimmer KA, Zottola MA, Sweeney RE, Graham JS Abstract We recently published electron paramagnetic resonance (EPR) spin trapping results that demonstrated the enzymatic reduction of sulfur mustard sulfonium ions to carbon-based free radicals using an in vitro system containing sulfur mustard, cytochrome P450 reductase, NADPH, and the spin trap α-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) in buffer (A.A. Brimfield et al., 2009, Toxicol. Appl. Pharmacol. 234:128-134). Carbon-based radicals have been shown to reduce molecular oxygen to form superoxide and, subsequently, peroxyl and hydroxyl radicals. In some cases, such as with the herbicide paraquat, a cyclic redox system results, leading to magnified oxygen free radical concentration and sustai... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5576767 Wed, 21 Dec 2011 05:00:00 +0100 5576767 http://www.medworm.com/index.php?rid=5576766&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206979%26dopt%3DAbstract Authors: Ji G, Gu A, Wang Y, Hu F, Huang C, Zhou Y, Song L, Wang X Abstract To test the hypothesis that polymorphisms in antioxidant genes are more susceptible to sperm DNA damage and male infertility, we examined 11 single-nucleotide polymorphisms from six antioxidant genes (GPX1, CAT, PON1, NQO1, SOD2/MnSOD, and SOD3) in 580 infertility cases and 580 controls from a Chinese population-based case-control study (NJMU Infertility Study). Genotypes were determined using the OpenArray platform. Sperm DNA fragmentation was detected using the Tdt-mediated dUTP nick-end labeling assay, and the level of 8-hydroxydeoxyguanosine (8-OHdG) in sperm DNA was measured using immunofluorescence. The adjusted odds ratio and 95% confidence interval (CI) were estimated using unconditional logistic re... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5576766 Wed, 21 Dec 2011 05:00:00 +0100 5576766 http://www.medworm.com/index.php?rid=5576765&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210352%26dopt%3DAbstract Authors: Wang L, Yang Z, Fu J, Yin H, Xiong K, Tan Q, Jin H, Li J, Wang T, Tang W, Yin J, Cai G, Liu M, Kehr S, Becker K, Zeng H Abstract Mammalian thioredoxin reductase 1 (TrxR1) is considered to be an important anticancer drug target and to be involved in both carcinogenesis and cancer progression. Here, we report that ethaselen, a novel organoselenium compound with anticancer activity, specifically binds to the unique selenocysteine-cysteine redox pair in the C-terminal active site of mammalian TrxR1. Ethaselen was found to be a potent inhibitor rather than an efficient substrate of mammalian TrxR1. It effectively inhibits wild-type mammalian TrxR1 at submicromolar concentrations with an initial mixed-type inhibition pattern. By using recombinant human TrxR1 variants and human g... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5576765 Wed, 21 Dec 2011 05:00:00 +0100 5576765 http://www.medworm.com/index.php?rid=5576763&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210380%26dopt%3DAbstract In this study, we sought to explore other potential mechanisms by which CORM-3 downregulates VCAM-1 expression on TNF-α-stimulated HUVECs. By genome-wide gene expression profiling and pathway analysis we studied the relevance of particular pathways for the anti-inflammatory effect of CORM-3. In CORM-3-stimulated HUVECs significant changes in expression were found for genes implicated in the proteasome and porphyrin pathways. Although proteasome activities were increased by CORM-3, proteasome inhibitors did not abolish the effect of CORM-3. Likewise, heme oxygenase-1 inhibitors did not abrogate the ability of CORM-3 to downregulate VCAM-1 expression. Interestingly, CORM-3 inhibited MAPK p38, and the p38 inhibitor SB203580 downregulated VCAM-1 expression. However, downregulation of VCAM-1 b... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5576763 Wed, 21 Dec 2011 05:00:00 +0100 5576763 http://www.medworm.com/index.php?rid=5576761&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22222468%26dopt%3DAbstract Authors: Mittal M, Gu XQ, Pak O, Pamenter ME, Haag D, Fuchs DB, Schermuly RT, Ghofrani HA, Brandes RP, Seeger W, Grimminger F, Haddad GG, Weissmann N Abstract There is current discussion whether reactive oxygen species are up- or downregulated in the pulmonary circulation during hypoxia, from which sources (i.e., mitochondria or NADPH oxidases) they are derived, and what the downstream targets of ROS are. We recently showed that the NADPH oxidase homolog NOX4 is upregulated in hypoxia-induced pulmonary hypertension in mice and contributes to the vascular remodeling in pulmonary hypertension. We here tested the hypothesis that NOX4 regulates K(v) channels via an increased ROS formation after prolonged hypoxia. We showed that (1) NOX4 is upregulated in hypoxia-induced pulmonary hyper... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5576761 Fri, 16 Dec 2011 05:00:00 +0100 5576761 http://www.medworm.com/index.php?rid=5544825&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198263%26dopt%3DAbstract In this study, we demonstrate the protective role of NQO1 in the development of emphysema using mouse models. NQO1-deficient animals demonstrated premature age-related emphysema and were more susceptible to both elastase and inhaled lipopolysaccharide models of emphysema. The absence of NQO1 was associated with enhanced markers of oxidant stress. Treatment of NQO1-deficient animals with the antioxidant N-acetylcysteine reversed the NQO1-dependent emphysematous changes. In vitro studies utilizing either inhibition or induction of NQO1 demonstrated a potent antioxidant role of NQO1 in macrophages, suggesting a role for macrophage-derived oxidants in the pathogenesis of emphysema. These novel findings support a functional role for NQO1 in protecting the lung from development of emphysema. ... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5544825 Fri, 16 Dec 2011 05:00:00 +0100 5544825 http://www.medworm.com/index.php?rid=5544824&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198267%26dopt%3DAbstract Authors: De Rasmo D, Signorile A, Larizza M, Pacelli C, Cocco T, Papa S Abstract A study of the relationship between cAMP/PKA-dependent phosphorylation and oxidative damage of subunits of complex I of the mitochondrial respiratory chain is presented. It is shown that, in fibroblast cultures, PKA-mediated phosphorylation of the NDUFS4 subunit of complex I rescues the activity of the oxidatively damaged complex. Evidence is presented showing that this effect is mediated by phosphorylation-dependent exchange of carbonylated NDUFS4 subunit in the assembled complex with the de novo synthesized subunit. These results indicate a potential use for β-adrenoceptor agonists in preventing/reversing the detrimental effects of oxidative stress in the mitochondrial respiratory system. PMID: ... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5544824 Fri, 16 Dec 2011 05:00:00 +0100 5544824 http://www.medworm.com/index.php?rid=5526669&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22182486%26dopt%3DAbstract Authors: Bedard K, Jaquet V, Krause KH Abstract In mammals, the NADPH oxidase family of enzymes comprises seven members: NOXs 1-5, DUOX1, and DUOX2. All of these enzymes function to move an electron across cellular membranes, transferring it to oxygen to generate the superoxide anion. This generation of reactive oxygen species has important physiological and pathophysiological roles. NOX5 is perhaps the least well understood of these NOX isoforms, in part because the gene is not present in mice or rats. In recent years, however, there has been a rapid increase in our understanding of the NOX5 gene, the structural and biochemical aspects of the NOX5 enzyme, the role NOX5 plays in health and disease, and the development of novel NOX inhibitors. This review takes a look back at some h... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526669 Wed, 14 Dec 2011 05:00:00 +0100 5526669 http://www.medworm.com/index.php?rid=5526830&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22155714%26dopt%3DAbstract In this study, we investigated the potential role of ATX in the response of microglial cells to oxidative stress. We show that treatment of a microglial BV2 cell line with hydrogen peroxide (H(2)O(2)) stimulates ATX expression and LPA production. Stable overexpression of ATX inhibits microglial activation (CD11b expression) and protects against H(2)O(2)-treatment-induced cellular damage. This protective effect of ATX was partially reduced in the presence of the LPA-receptor antagonist Ki16425. ATX overexpression was also associated with a reduction in intracellular ROS formation, carbonylated protein accumulation, proteasomal activity, and catalase expression. Our results suggest that up-regulation of ATX expression in microglia could be a mechanism for protection against oxidative stress,... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526830 Thu, 08 Dec 2011 05:00:00 +0100 5526830 http://www.medworm.com/index.php?rid=5526718&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172527%26dopt%3DAbstract Authors: Belkacemi A, Ramassamy C Abstract Alzheimer disease (AD) is a multifactorial disorder characterized by the presence of amyloid plaques and neurofibrillary tangles (NFTs). Rare early-onset forms of AD are associated with autosomal dominant mutations in the amyloid precursor protein gene, presenilin 1 gene, or presenilin 2 gene. The late-onset form of the disease (LOAD) is the most common form. The causes of LOAD are not yet clarified, but several environmental and genetic risk factors have been identified. Numerous studies have highlighted a role for free radical-mediated injury to brain regions of this illness. In addition, studies from mild cognitive impairment patients suggest that oxidative stress is an early event in the pathogenesis of AD. The associations between the... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526718 Thu, 08 Dec 2011 05:00:00 +0100 5526718 http://www.medworm.com/index.php?rid=5526679&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178414%26dopt%3DAbstract Authors: Pazmandi K, Magyarics Z, Boldogh I, Csillag A, Rajnavolgyi E, Bacsi A Abstract Under normal conditions, plasmacytoid dendritic cells (pDC's) are located in peripheral lymphoid organs or circulate in the blood, from where they can migrate to sites of infection or inflammation. In inflamed tissues, pDC's can be exposed to elevated levels of reactive oxygen species produced by inflammatory cells and we presume that oxidative stress could affect the cellular responses of pDC's to microenvironmental stimuli. To explore this possibility, human pDC's isolated from peripheral blood of healthy donors were treated with H(2)O(2) and R837 (a Toll-like receptor 7 ligand), separately and in combination. Our results demonstrate that treatment with a low concentration (0.01μM) of H(2)O(2... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526679 Thu, 08 Dec 2011 05:00:00 +0100 5526679 http://www.medworm.com/index.php?rid=5526671&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178978%26dopt%3DAbstract Authors: Swalwell H, Latimer J, Haywood RM, Birch-Machin MA Abstract Skin cancer incidence is dramatically increasing worldwide, with exposure to ultraviolet radiation (UVR) a predominant factor. The UVA component initiates oxidative stress in human skin, although its exact role in the initiation of skin cancer, particularly malignant melanoma, remains unclear and is controversial because there is evidence for a melanin-dependent mechanism in UVA-linked melanoma studies. Nonpigmented (CHL-1, A375), moderately pigmented (FM55, SKmel23), and highly pigmented (FM94, hyperpigmented FM55) human melanoma cell lines have been used to investigate UVA-induced production of reactive oxygen species using FACS analysis, at both the cellular (dihydrorhodamine-123) and the mitochondrial (MitoSOX... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526671 Thu, 08 Dec 2011 05:00:00 +0100 5526671 http://www.medworm.com/index.php?rid=5526670&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178979%26dopt%3DAbstract Authors: Yu CC, Nandrot EF, Dun Y, Finnemann SC Abstract In the aging human eye, oxidative damage and accumulation of pro-oxidant lysosomal lipofuscin cause functional decline of the retinal pigment epithelium (RPE), which contributes to age-related macular degeneration. In mice with an RPE-specific phagocytosis defect due to lack of αvβ5 integrin receptors, RPE accumulation of lipofuscin suggests that the age-related blindness we previously described in this model may also result from oxidative stress. Cellular and molecular targets of oxidative stress in the eye remain poorly understood. Here we identify actin among 4-hydroxynonenal (HNE) adducts formed specifically in β5(-/-) RPE but not in neural retina with age. HNE modification directly correlated with loss of resistance o... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526670 Thu, 08 Dec 2011 05:00:00 +0100 5526670 http://www.medworm.com/index.php?rid=5526833&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22155056%26dopt%3DAbstract Authors: Oh CJ, Kim JY, Min AK, Park KG, Harris RA, Kim HJ, Lee IK Abstract Sulforaphane (SFN) is a dietary isothiocyanate that exerts chemopreventive effects via NF-E2-related factor 2 (Nrf2)-mediated induction of antioxidant/phase II enzymes, such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). This work was undertaken to evaluate the effects of SFN on hepatic fibrosis and profibrotic transforming growth factor (TGF)-β/Smad signaling, which are closely associated with oxidative stress. SFN suppressed TGF-β-enhanced expression of α-smooth muscle actin (α-SMA), a marker of hepatic stellate cell (HSC) activation, and profibrogenic genes such as type I collagen, fibronectin, tissue inhibitor of matrix metalloproteinase-1, and plasminogen activator inhibito... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526833 Thu, 01 Dec 2011 05:00:00 +0100 5526833 http://www.medworm.com/index.php?rid=5526831&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22155057%26dopt%3DAbstract Authors: Gu X, Salomon RG Abstract Many of the pathological effects of lipid peroxidation are mediated by aldehydes generated through fragmentation of lipid peroxides. Among these aldehydes, the γ-hydroxy- and γ-oxo-α,β-alkenals, e.g., 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE), are especially prone to modifying proteins and DNA through covalent adduction. In addition the "mirror image" γ-hydroxy- and γ-oxo-α,β-alkenal phospholipids can serve as high-affinity ligands for biological receptors triggering pathology. Therefore, the mechanisms by which these aldehydes are generated in vivo are under intense scrutiny. We now report observations supporting the intermediacy of a unique pseudo-symmetrical diepoxycarbinyl radical that accounts for the coproduction of HNE, ON... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526831 Thu, 01 Dec 2011 05:00:00 +0100 5526831 http://www.medworm.com/index.php?rid=5526683&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178413%26dopt%3DAbstract Authors: Jädert C, Petersson J, Massena S, Ahl D, Grapensparr L, Holm L, Lundberg JO, Phillipson M Abstract Nitric oxide (NO) generated by vascular NO synthases can exert anti-inflammatory effects, partly through its ability to decrease leukocyte recruitment. Inorganic nitrate and nitrite, from endogenous or dietary sources, have emerged as alternative substrates for NO formation in mammals. Bioactivation of nitrate is believed to require initial reduction to nitrite by oral commensal bacteria. Here we investigated the effects of inorganic nitrate and nitrite on leukocyte recruitment in microvascular inflammation and in NSAID-induced small-intestinal injury. We show that leukocyte emigration in response to the proinflammatory chemokine MIP-2 is reduced by 70% after 7days of dietar... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526683 Wed, 30 Nov 2011 05:00:00 +0100 5526683 http://www.medworm.com/index.php?rid=5526673&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178976%26dopt%3DAbstract In this study, we evaluated the effect of purple sweet potato color on cognitive deficits induced by hippocampal mitochondrial dysfunction in domoic acid-treated mice and explored the potential mechanisms underlying this effect. Our results showed that the oral administration of purple sweet potato color to domoic acid-treated mice significantly improved their behavioral performance in a step-through passive avoidance task and a Morris water maze task. These improvements were mediated, at least in part, by a stimulation of estrogen receptor-α-mediated mitochondrial biogenesis signaling and by decreases in the expression of p47phox and gp91phox. Decreases in reactive oxygen species and protein carbonylation were also observed, along with a blockade of the endoplasmic reticulum stress pathw... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526673 Wed, 23 Nov 2011 05:00:00 +0100 5526673 http://www.medworm.com/index.php?rid=5526829&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172526%26dopt%3DAbstract Authors: Sourris KC, Harcourt BE, Tang PH, Morley AL, Huynh K, Penfold SA, Coughlan MT, Cooper ME, Nguyen TV, Ritchie RH, Forbes JM Abstract Cardiovascular benefits of ubiquinone have been previously demonstrated, and we administered it as a novel therapy in an experimental model of type 2 diabetic nephropathy. db/db and dbH mice were followed for 10weeks, after randomization to receive either vehicle or ubiquinone (CoQ10; 10mg/kg/day) orally. db/db mice had elevated urinary albumin excretion rates and albumin:creatinine ratio, not seen in db/db CoQ10-treated mice. Renal cortices from db/db mice had lower total and oxidized CoQ10 content, compared with dbH mice. Mitochondria from db/db mice also contained less oxidized CoQ10(ubiquinone) compared with dbH mice. Diabetes-induced incr... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526829 Mon, 21 Nov 2011 05:00:00 +0100 5526829 http://www.medworm.com/index.php?rid=5526834&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22154654%26dopt%3DAbstract Authors: Rocha BS, Gago B, Barbosa RM, Lundberg JO, Radi R, Laranjinha J Abstract Inorganic nitrite, derived from the reduction of nitrate in saliva, has recently emerged as a protagonist in nitric oxide ((•)NO) biology as it can be univalently reduced to (•)NO, in the healthy human stomach. Important physiological implications have been attributed to nitrite-derived (•)NO in the gastrointestinal tract, namely modulation of host defense, blood flow, mucus formation and motility. At acidic pH, nitrite generates different nitrogen oxides depending on the local microenvironment (redox status, gastric content, pH, inflammatory conditions), including (•)NO, nitrogen dioxide ((•)NO(2)), dinitrogen trioxide (N(2)O(3)), and peroxynitrite. Thus, the gastric environment is a signif... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526834 Sun, 20 Nov 2011 05:00:00 +0100 5526834 http://www.medworm.com/index.php?rid=5526712&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178412%26dopt%3DAbstract In conclusion, lycopene may be beneficial for treatment of H. pylori-induced gastric diseases associated with oxidative DNA damage. PMID: 22178412 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine) Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526712 Sun, 20 Nov 2011 05:00:00 +0100 5526712 http://www.medworm.com/index.php?rid=5526857&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22101009%26dopt%3DAbstract Authors: Silkstone RS, Mason MG, Nicholls P, Cooper CE Abstract We previously reported that high micromolar concentrations of nitric oxide were able to oxidize mitochondrial cytochrome c at physiological pH, producing nitroxyl anion (Sharpe and Cooper, 1998 Biochem. J. 332, 9-19). However, the subsequent re-evaluation of the redox potential of the NO/NO(-) couple suggests that this reaction is thermodynamically unfavored. We now show that the oxidation is oxygen-concentration dependent and non stoichiometric. We conclude that the effect is due to an oxidant species produced during the aerobic decay of nitric oxide to nitrite and nitrate. The species is most probably nitrogen dioxide, NO(2)(•) a well-known biologically active oxidant. A simple kinetic model of NO autoxidation is a... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526857 Thu, 17 Nov 2011 05:00:00 +0100 5526857 http://www.medworm.com/index.php?rid=5526672&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178977%26dopt%3DAbstract Authors: Escobar J, Pereda J, López-Rodas G, Sastre J Abstract Histone acetylation via CBP/p300 coordinates the expression of proinflammatory cytokines in the activation phase of inflammation, particularly through mitogen-activated protein kinases (MAPKs), nuclear factor-κB (NF-κB), and signal transducers and activators of transcription pathways. In contrast, histone deacetylases (HDACs) and protein phosphatases are mainly involved in the attenuation phase of inflammation. The role of reactive oxygen species (ROS) in the inflammatory cascade is much more important than expected. Mitochondrial ROS act as signal-transducing molecules that trigger proinflammatory cytokine production via inflammasome-independent and inflammasome-dependent pathways. The major source of ROS in acute i... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526672 Wed, 16 Nov 2011 05:00:00 +0100 5526672 http://www.medworm.com/index.php?rid=5526836&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22142474%26dopt%3DAbstract Authors: Pantaleo A, Ferru E, Vono R, Giribaldi G, Lobina O, Nepveu F, Ibrahim H, Nallet JP, Carta F, Mannu F, Pippia P, Campanella E, Low PS, Turrini F Abstract Although long-lived radicals formed from indolone-N-oxide derivatives (INODs) possess antiplasmodial activity in the low-nanomolar range, little is known about their mechanism of action. To explore the molecular basis of INOD activity, we screened for changes in INOD-treated malaria-infected erythrocytes (Pf-RBCs) using a proteomics approach. At early parasite maturation stages, treatment with INODs at their IC(50) concentrations induced a marked tyrosine phosphorylation of the erythrocyte membrane protein band 3, whereas no effect was observed in control RBCs. After INOD treatment of Pf-RBCs we also observed: (i) accelera... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526836 Tue, 15 Nov 2011 05:00:00 +0100 5526836 http://www.medworm.com/index.php?rid=5526838&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22142472%26dopt%3DAbstract Authors: Enomoto A, Kido N, Ito M, Takamatsu N, Miyagawa K Abstract Serine-threonine kinase 38 (STK38) is a member of the protein kinase A (PKA)/PKG/PKC-like family. In the present study, we investigated the regulatory mechanism of STK38 and assessed its role in the cellular stress response. Among various environmental stresses, STK38 was specifically activated by H(2)O(2), and the phosphatidylinositol 3-kinase inhibitor wortmannin or AKT inhibitor IV suppressed this activation. STK38 was also activated by a constitutively active AKT1 or by GSK-3β inhibitor VII. The phosphorylation level of GSK-3β was correlated with the STK38 activity, in response to various stimuli and in different cell lines. Co-immunoprecipitation analysis revealed that GSK-3β physically interacted with STK3... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526838 Sun, 13 Nov 2011 05:00:00 +0100 5526838 http://www.medworm.com/index.php?rid=5526837&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22142473%26dopt%3DAbstract Authors: Furfaro AL, Macay JR, Marengo B, Nitti M, Parodi A, Fenoglio D, Marinari UM, Pronzato MA, Domenicotti C, Traverso N Abstract Cancer cell survival is known to be related to the ability to counteract oxidative stress, and glutathione (GSH) depletion has been proposed as a mechanism to sensitize cells to anticancer therapy. However, we observed that GI-ME-N cells, a neuroblastoma cell line without MYCN amplification, are able to survive even if GSH-depleted by l-buthionine-(S,R)-sulfoximine (BSO). Here, we show that in GI-ME-N cells, BSO activates Nrf2 and up-regulates heme oxygenase-1 (HO-1). Silencing of Nrf2 restrained HO-1 induction by BSO. Inhibition of HO-1 and silencing of Nrf2 or HO-1 sensitized GI-ME-N cells to BSO, leading to reactive oxygen/nitrogen species overpro... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526837 Sun, 13 Nov 2011 05:00:00 +0100 5526837 http://www.medworm.com/index.php?rid=5526841&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22137893%26dopt%3DAbstract In this study, brain tissue from AD and control patients was examined by immunocytochemistry and immunoelectron microscopy for evidence of HNE-crosslinking modifications of the type that should accumulate in the lipofuscin pathway. Strong labeling of granulovacuolar degeneration (GVD) and Hirano bodies was noted but lipofuscin did not contain this specific HNE-fluorophore. These findings directly implicate lipid crosslinking peroxidation products as accumulating not in the lesions or the lipofuscin pathways, but instead in a distinct pathway, GVD, that accumulates cytosolic proteins. PMID: 22137893 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine) Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526841 Sat, 12 Nov 2011 05:00:00 +0100 5526841 http://www.medworm.com/index.php?rid=5526839&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22142471%26dopt%3DAbstract In this study, the cancer-chemopreventive agent nordihydroguaiaretic acid (NDGA) increased the level of Nrf2 protein and expression of heme oxygenase-1 (HO-1) in kidney-derived LLC-PK1 and HEK293T cells and in wild-type mouse embryo fibroblasts (MEFs). However, NDGA did not induce HO-1 in Nrf2(-/-) MEFs, indicating that Nrf2 is required for induction. The relevance of the Nrf2/HO-1 axis to antioxidant protection was further demonstrated by the finding that the HO-1 inhibitor stannous-mesoporphyrin abolished protection against hydrogen peroxide conferred by NDGA. NDGA increased Nrf2 and HO-1 protein levels in Keap1(-/-) MEFs, implying that Keap1-independent mechanisms regulate Nrf2 stability. Mutants of the Neh2 or Nrh6 domain and chimeric proteins comprising cyan fluorescent protein fused ... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526839 Sat, 12 Nov 2011 05:00:00 +0100 5526839 http://www.medworm.com/index.php?rid=5526835&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22154653%26dopt%3DAbstract Authors: Kvietys PR, Granger DN Abstract Inflammation is a complex and potentially life-threatening condition that involves the participation of a variety of chemical mediators, signaling pathways, and cell types. The microcirculation, which is critical for the initiation and perpetuation of an inflammatory response, exhibits several characteristic functional and structural changes in response to inflammation. These include vasomotor dysfunction (impaired vessel dilation and constriction), the adhesion and transendothelial migration of leukocytes, endothelial barrier dysfunction (increased vascular permeability), blood vessel proliferation (angiogenesis), and enhanced thrombus formation. These diverse responses of the microvasculature largely reflect the endothelial cell dysfunctio... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526835 Sat, 12 Nov 2011 05:00:00 +0100 5526835 http://www.medworm.com/index.php?rid=5526842&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22120895%26dopt%3DAbstract Authors: Faller P PMID: 22120895 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine) Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526842 Fri, 11 Nov 2011 05:00:00 +0100 5526842 http://www.medworm.com/index.php?rid=5526844&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22120494%26dopt%3DAbstract Authors: Mukhopadhyay P, Horváth B, Zsengellér Z, Zielonka J, Tanchian G, Holovac E, Kechrid M, Patel V, Stillman IE, Parikh SM, Joseph J, Kalyanaraman B, Pacher P Abstract Cisplatin is a widely used antineoplastic agent; however, its major limitation is the development of dose-dependent nephrotoxicity whose precise mechanisms are poorly understood. Here we show not only that mitochondrial dysfunction is a feature of cisplatin nephrotoxicity, but also that targeted delivery of superoxide dismutase mimetics to mitochondria largely prevents the renal effects of cisplatin. Cisplatin induced renal oxidative stress, deterioration of mitochondrial structure and function, an intense inflammatory response, histopathological injury, and renal dysfunction. A single systemic dose of mitocho... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526844 Thu, 10 Nov 2011 05:00:00 +0100 5526844 http://www.medworm.com/index.php?rid=5526840&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22138102%26dopt%3DAbstract In this report, we demonstrate that although Cobl can be an excellent antioxidant, exposure to high levels of HOCl can overcome the beneficial effects of Cobl and generate proinflammatory reaction products. Our rapid kinetic, HPLC, and mass spectrometric analyses showed that HOCl can mediate corrin ring destruction and liberate cyanogen chloride (CNCl) through a mechanism that initially involves α-axial ligand replacement in Cobl to form a chlorinated derivative, hydrolysis, and cleavage of the phosphonucleotide moiety. Additionally, it can liberate free Co, which can perpetuate metal-ion-induced oxidant stress. Taken together, these results are the first report of the generation of toxic molecular products through the interaction of Cobl with HOCl. PMID: 22138102 [PubMed - as supplie... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526840 Thu, 10 Nov 2011 05:00:00 +0100 5526840 http://www.medworm.com/index.php?rid=5526845&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22115789%26dopt%3DAbstract Authors: Wilkins HM, Marquardt K, Lash LH, Linseman DA Abstract Despite making up only a minor fraction of the total cellular glutathione, recent studies indicate that the mitochondrial glutathione pool is essential for cell survival. Selective depletion of mitochondrial glutathione is sufficient to sensitize cells to mitochondrial oxidative stress (MOS) and intrinsic apoptosis. Glutathione is synthesized exclusively in the cytoplasm and must be actively transported into mitochondria. Therefore, regulation of mitochondrial glutathione transport is a key factor in maintaining the antioxidant status of mitochondria. Bcl-2 resides in the outer mitochondrial membrane where it acts as a central regulator of the intrinsic apoptotic cascade. In addition, Bcl-2 displays an antioxidant-like... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526845 Wed, 09 Nov 2011 05:00:00 +0100 5526845 http://www.medworm.com/index.php?rid=5526843&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22120495%26dopt%3DAbstract Authors: Chaiswing L, Zhong W, Liang Y, Jones DP, Oberley TD Abstract Recent metabolic profiles of human prostate cancer tissues showed a significant increase in cysteine (Cys) and a significant decrease in reduced glutathione (GSH) during cancer progression from low- to high-grade Gleason scores. Cys is primarily localized extracellularly, whereas GSH is present mostly inside the cell. We hypothesized that extra- or intracellular redox state alterations differentially regulate cell invasion in PC3 prostate carcinoma cells versus PrEC normal prostate epithelial cells. Cells were exposed to media with calculated Cys/CySS redox potentials (E(h)CySS) ranging from -60 to -180mV. After 3h exposure to a reducing extracellular redox state (E(h)CySS=-180mV), matrix metalloprotease (MMP), g... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526843 Wed, 09 Nov 2011 05:00:00 +0100 5526843 http://www.medworm.com/index.php?rid=5526873&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100972%26dopt%3DAbstract Authors: Giedt RJ, Yang C, Zweier JL, Matzavinos A, Alevriadou BR Abstract Ischemia (I)/reperfusion (RP)-induced endothelial cell (EC) injury is thought to be due to mitochondrial reactive oxygen species (mtROS) production. MtROS have been implicated in mitochondrial fission. We determined whether cultured EC exposure to simulated I/RP causes morphological changes in the mitochondrial network and the mechanisms behind those changes. Because shear stress results in nitric oxide (NO)-mediated endothelial mtROS generation, we simulated I/RP as hypoxia (H) followed by oxygenated flow over the ECs (shear stress of 10dyn/cm(2)). By exposing ECs to shear stress, H, H/reoxygenation (RO), or simulated I/RP and employing MitoTracker staining, we assessed the differential effects of changes i... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526873 Sun, 06 Nov 2011 04:00:00 +0100 5526873 http://www.medworm.com/index.php?rid=5526847&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22107958%26dopt%3DAbstract Authors: Raval CM, Zhong J, Mitchell SA, Tyrrell RM Abstract Up-regulation of heme oxygenase 1 (HO-1) by ultraviolet A (UVA; 320-380nm) irradiation of human skin cells protects them against oxidative stress. The role of Nrf2 in up-regulation of HO-1 and other phase II genes is well established. The mechanism underlying Bach1-mediated HO-1 repression is less well understood although cellular localization seems to be crucial. Because prolonged HO-1 overexpression is likely to be detrimental, it is crucial that activation of the gene is transient. We now show that UVA irradiation of cultured human skin fibroblasts enhances accumulation of Bach1 mRNA and protein severalfold. Endogenous Bach1 protein accumulates in the nucleus after 8h and may occupy MARE sites after HO-1 activation thu... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526847 Sun, 06 Nov 2011 04:00:00 +0100 5526847 http://www.medworm.com/index.php?rid=5526875&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100504%26dopt%3DAbstract Authors: Carneiro P, Duarte M, Videira A Abstract Mitochondria are a main providers of high levels of energy, but also a major source of reactive oxygen species (ROS) during normal oxidative metabolism. The involvement of Neurospora crassa alternative NAD(P)H dehydrogenases in mitochondrial ROS production was evaluated. The growth responses of a series of respiratory mutants to several stress conditions revealed that disrupting alternative dehydrogenases leads to an increased tolerance to the redox cycler paraquat, with a mutant devoid of the external NDE1 and NDE2 enzymes being significantly more resistant. The nde1nde2 mutant mitochondria show a significant decrease in ROS generation in the presence and absence of paraquat, regardless of the respiratory substrate used, and an int... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526875 Fri, 04 Nov 2011 04:00:00 +0100 5526875 http://www.medworm.com/index.php?rid=5526874&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100505%26dopt%3DAbstract Authors: Scarbrough PM, Mapuskar KA, Mattson DM, Gius D, Watson WH, Spitz DR Abstract 17-Allylamino-17-demethoxygeldanamycin (17AAG) is an experimental chemotherapeutic agent believed to form free radicals in vivo, and cancer cell resistance to 17AAG is believed to be a thiol-dependent process. Inhibitors of thiol-dependent hydroperoxide metabolism [l-buthionine-S,R-sulfoximine (BSO) and auranofin] were combined with the glucose metabolism inhibitor 2-deoxy-d-glucose (2DG) to determine if 17AAG-mediated cancer cell killing could be enhanced. When 2DG (20mM, 24h), BSO (1mM, 24h), and auranofin (500nM, 3h) were combined with 17AAG, cell killing was significantly enhanced in three human cancer cell lines (PC-3, SUM159, MDA-MB-231). Furthermore, the toxicity of this drug combination wa... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526874 Fri, 04 Nov 2011 04:00:00 +0100 5526874 http://www.medworm.com/index.php?rid=5526878&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22094224%26dopt%3DAbstract This study investigated the mechanism behind TMZ-induced cell death and the possibility that resveratrol might increase TMZ efficacy. TMZ induced both apoptotic cell death and cytoprotective autophagy through a reactive oxygen species (ROS) burst and extracellular signal-regulated kinase (ERK) activation, which was suppressed by resveratrol, resulting in a decrease in autophagy and an increase in apoptosis, suggesting that the ROS/ERK pathway plays a crucial role in the fate of cells after TMZ treatment. Isobolographic analysis indicated that the combination of TMZ and resveratrol has a synergistic effect. Moreover, an in vivo mouse xenograft study also showed that coadministration of resveratrol and TMZ reduced tumor volumes by suppressing ROS/ERK-mediated autophagy and subsequently induc... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526878 Thu, 03 Nov 2011 04:00:00 +0100 5526878 http://www.medworm.com/index.php?rid=5526877&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22094225%26dopt%3DAbstract In conclusion, rotenone directly interacted with gp91(phox); such an interaction triggered membrane translocation of p67(phox), leading to PHOX activation and superoxide production. PMID: 22094225 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine) Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526877 Thu, 03 Nov 2011 04:00:00 +0100 5526877 http://www.medworm.com/index.php?rid=5526876&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100343%26dopt%3DAbstract This study was designed to test a hypothesis that the CD38/cADPR pathway as a downstream event exerts feedback regulatory action on the NAD(P)H oxidase activity in production of extra- or intracellular O(2)(•-) in mouse coronary arterial myocytes (CAMs). By fluorescence microscopic imaging, we simultaneously monitored extra- and intracellular O(2)(•-) production in wild-type (CD38(+/+)) and CD38 knockout (CD38(-/-)) CAMs in response to oxotremorine (OXO), a muscarinic type 1 receptor agonist. It was found that CD38 deficiency prevented OXO-induced intracellular but not extracellular O(2)(•-) production in CAMs. Consistently, the OXO-induced intracellular O(2)(•-) production was markedly inhibited by CD38 shRNA or the CD38 inhibitor nicotinamide in CD38(+/+) CAMs. Further, Nox4 siRN... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526876 Thu, 03 Nov 2011 04:00:00 +0100 5526876 http://www.medworm.com/index.php?rid=5526872&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100973%26dopt%3DAbstract Authors: Li G, Yuan K, Yan C, Fox J, Gaid M, Breitwieser W, Bansal AK, Zeng H, Gao H, Wu M Abstract 8-Oxoguanine-DNA glycosylase (OGG-1) is a base excision DNA repair enzyme; however, its function in modulating allergic diseases remains undefined. Using OGG-1 knockout (KO) mice, we show that this protein affects allergic airway inflammation after sensitization and challenge by ovalbumin(OVA). OGG-1 KO mice exhibited less inflammatory cell infiltration and reduced oxidative stress in the lungs after OVA challenge compared to WT mice. The KO phenotype included decreased IL-4, IL-6, IL-10, and IL-17 in lung tissues. In addition, OGG-1 KO mice showed decreased expression and phosphorylation of STAT6 as well as NF-κB. Down-regulation of OGG-1 by siRNA lowered ROS and IL-4 levels but in... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526872 Thu, 03 Nov 2011 04:00:00 +0100 5526872 http://www.medworm.com/index.php?rid=5526846&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22107959%26dopt%3DAbstract We describe the structure-activity relationships for a series of peptides based upon regions of the Nrf2 Neh2 domain, of varying length and sequence, that interact with the Keap1 Kelch domain and disrupt the interaction with Nrf2. We have also investigated sequestosome-1 (p62) and prothymosin-α sequences that have been reported to interact with Keap1. To achieve this we have developed a high-throughput fluorescence polarization (FP) assay to screen inhibitors. In addition to screening synthetic peptides, we have used a phage display library approach to identify putative peptide ligands with non-native sequence motifs. Candidate peptides from the phage display library screening protocol were evaluated in the FP assay to quantify their binding activity. Hybrid peptides based upon the Nrf2 "... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5526846 Thu, 03 Nov 2011 04:00:00 +0100 5526846 http://www.medworm.com/index.php?rid=5414100&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22080085%26dopt%3DAbstract Authors: Octavia Y, Brunner-La Rocca HP, Moens AL Abstract Heart failure (HF) occurs when the adaptation mechanisms of the heart fail to compensate for stress factors, such as pressure overload, myocardial infarction, inflammation, diabetes, and cardiotoxic drugs, with subsequent ventricular hypertrophy, fibrosis, myocardial dysfunction, and chamber dilatation. Oxidative stress, defined as an imbalance between reactive oxygen species (ROS) generation and the capacity of antioxidant defense systems, has been authenticated as a pivotal player in the cardiopathogenesis of the various HF subtypes. The family of NADPH oxidases has been investigated as a key enzymatic source of ROS in the pathogenesis of HF. In this review, we discuss the importance of NADPH oxidase-dependent ROS generat... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5414100 Thu, 03 Nov 2011 04:00:00 +0100 5414100 http://www.medworm.com/index.php?rid=5294218&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21971348%26dopt%3DAbstract In this study, we analyzed the effects of the two drugs on liver mitochondrial function by administering an equivalent human dose to a rat model. Amiodarone increased mitochondrial H(2)O(2) synthesis, which in turn induced cardiolipin peroxidation. Moreover, amiodarone inhibited Complex I activity and uncoupled oxidative phosphorylation, leading to a reduction in the hepatic ATP content. We also observed a modification of membrane phospholipid composition after amiodarone administration. N-acetylcysteine completely prevented such effects. Although dronedarone shares with amiodarone the capacity to induce uncoupling of oxidative phosphorylation, it did not show any of the oxidative effects and did not impair mitochondrial bioenergetics. Our data provide important insights into the mechanism... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5294218 Sat, 17 Sep 2011 04:00:00 +0100 5294218 http://www.medworm.com/index.php?rid=5294232&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21963991%26dopt%3DAbstract Authors: Miura T, Shinkai Y, Hirose R, Iwamoto N, Cho AK, Kumagai Y Abstract 1,2-Naphthoquinone (1,2-NQ) is electrophilic, and forms covalent bonds with protein thiols, but its two-electron reduction product 1,2-dihydroxynaphthalene (1,2-NQH(2)) is not, so enzymes catalyzing the reduction with reduced pyridine nucleotides as cofactors could protect cells from electrophile-based chemical insults. To assess this possibility, we examined proteins isolated from the 9000g supernatant from mouse liver for 1,2-NQ reductase activity using an HPLC assay procedure for the hydroquinone of 1,2-NQ and Cibacron Blue 3GA column chromatography and Western blot analysis with specific antibody to determine 1,2-NQ-bound proteins. Among the proteins with high affinities for pyridine nucleotides that a... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5294232 Fri, 16 Sep 2011 04:00:00 +0100 5294232 http://www.medworm.com/index.php?rid=5294221&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21964506%26dopt%3DAbstract In conclusion, we demonstrate that butein and phloretin up-regulate HO-1 and GCL expression through the ERK2/Nrf2 pathway and protect hepatocytes against oxidative stress. PMID: 21964506 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine) Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5294221 Fri, 16 Sep 2011 04:00:00 +0100 5294221 http://www.medworm.com/index.php?rid=5294219&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21971347%26dopt%3DAbstract In this study we further investigated the interaction between XRCC5 and Cu. We report that cytosolic XRCC5 is increased in response to Cu, but not zinc, iron, or nickel, and the level of cytosolic XRCC5 correlates with protection against oxidative damage to DNA. These observations were made in both HeLa cells and fibroblasts. Cytosolic XRCC5 interacted with the Cu chaperone and detoxification protein human Atox1 homologue (HAH), and down regulation of XRCC5 expression using siRNA led to enhanced HAH expression when cells were exposed to Cu. XRCC5 could also be purified from cytosolic extracts using a Cu-loaded column. These findings provide further evidence that cytosolic XRCC5 has a key role in protection against DNA oxidation from Cu, through either direct sequestration or signaling thro... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5294219 Fri, 16 Sep 2011 04:00:00 +0100 5294219 http://www.medworm.com/index.php?rid=5294233&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21963990%26dopt%3DAbstract In this study, we expressed low levels of CYP3A4 in HepG2 cells, a human hepatocarcinoma cell line, and examined effects on intracellular levels of ROS and on the secretion of a variety of growth factors that are important in extracellular communication. Using the redox-sensitive dye RedoxSensor red, we demonstrate that CYP3A4 expression increases levels of ROS in viable cells. A custom ELISA microarray platform was employed to demonstrate that expression of CYP3A4 increased secretion of amphiregulin, intracellular adhesion molecule 1, matrix metalloprotease 2, platelet-derived growth factor (PDGF), and vascular endothelial growth factor, but suppressed secretion of CD14. The antioxidant N-acetylcysteine suppressed all P450-dependent changes in protein secretion except for CD14. Quantitati... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5294233 Sat, 10 Sep 2011 04:00:00 +0100 5294233 http://www.medworm.com/index.php?rid=5294231&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21964033%26dopt%3DAbstract We report here, using mitochondria from muscle creatine kinase-PGC-1α transgenic mice, that PGC-1α does not affect the topology of ROS production, but increases the capacity of complexes I and III to generate ROS. These changes are associated with increased mitochondrial respiration and content of respiratory chain complexes. When normalizing ROS production to mitochondrial respiration, we find that PGC-1α preserves the percentage of free radical leak by the electron transport chain. Together, these data demonstrate that PGC-1α regulates the intrinsic properties of mitochondria in such a way as to preserve a tight coupling between mitochondrial respiration and ROS production. PMID: 21964033 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine) Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5294231 Sat, 10 Sep 2011 04:00:00 +0100 5294231 http://www.medworm.com/index.php?rid=5294230&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21964034%26dopt%3DAbstract Authors: Morgan B, Sobotta MC, Dick TP Abstract Redox biochemistry plays an important role in a wide range of cellular events. However, investigation of cellular redox processes is complicated by the large number of cellular redox couples, which are often not in equilibrium with one another and can vary significantly between subcellular compartments and cell types. Further, it is becoming increasingly clear that different redox systems convey different biological information; thus it makes little sense to talk of an overall "cellular redox state." To gain a more differentiated understanding of cellular redox biology, quantitative, redox couple-specific, in vivo measurements are necessary. Unfortunately our ability to investigate specific redox couples or redox-reactive molecules wi... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5294230 Sat, 10 Sep 2011 04:00:00 +0100 5294230 http://www.medworm.com/index.php?rid=5294220&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21964507%26dopt%3DAbstract In this study, we found that glucocorticoid treatment of WEHI7.2 murine thymic lymphoma cells increased the steady-state [H(2)O(2)] and oxidized the intracellular redox environment before cytochrome c release. Removal of glucocorticoids after the H(2)O(2) increase resulted in a 30% clonogenicity; treatment with PEG-CAT increased clonogenicity to 65%. Human leukemia cell lines also showed increased H(2)O(2) in response to glucocorticoids and attenuated apoptosis after PEG-CAT treatment. WEHI7.2 cells that overexpress catalase (CAT2, CAT38) or were selected for resistance to H(2)O(2) (200R) removed enough of the H(2)O(2) generated by glucocorticoids to prevent oxidation of the intracellular redox environment. CAT2, CAT38, and 200R cells showed a 90-100% clonogenicity. The resistant cells mai... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5294220 Sat, 10 Sep 2011 04:00:00 +0100 5294220 http://www.medworm.com/index.php?rid=5273267&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21958548%26dopt%3DAbstract Authors: Robinson MA, Baumgardner JE, Otto CM Abstract Inducible nitric oxide synthase (iNOS) catalyzes the reaction that converts the substrates O(2) and l-arginine to the products nitric oxide (NO) and l-citrulline. Macrophages, and many other cell types, upregulate and express iNOS primarily in response to inflammatory stimuli. Physiological and pathophysiological oxygen tension can regulate NO production by iNOS at multiple levels, including transcriptional, translational, posttranslational, enzyme dimerization, cofactor availability, and substrate dependence. Cell culture techniques that emphasize control of cellular PO(2), and measurement of NO or its stable products, have been used by several investigators for in vitro study of the O(2) dependence of NO production at one or ... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5273267 Thu, 08 Sep 2011 04:00:00 +0100 5273267 http://www.medworm.com/index.php?rid=5273272&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945096%26dopt%3DAbstract Authors: Murley JS, Baker KL, Miller RC, Darga TE, Weichselbaum RR, Grdina DJ Abstract Manganese superoxide dismutase (SOD2)-mediated adaptive processes that protect against radiation-induced micronucleus formation can be induced in cells after a 2-Gy exposure by previously exposing them to either low-dose ionizing radiation (10cGy) or WR1065 (40μM), the active thiol form of amifostine. Although both adaptive processes culminate in elevated levels of SOD2 enzymatic activity, the underlying pathways differ in complexity, with the tumor necrosis factor α (TNFα) signaling pathway implicated in the low-dose radiation-induced response, but not in the thiol-induced pathway. The goal of this study was the characterization of the effects of TNFα receptors 1 and 2 (TNFR1, TNFR2) on the ... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5273272 Sat, 03 Sep 2011 04:00:00 +0100 5273272 http://www.medworm.com/index.php?rid=5273269&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945367%26dopt%3DAbstract Authors: Traber MG, Labut EM, Leonard SW, Lebold KM Abstract The role of hepatic xenobiotic regulatory mechanisms in modulating hepatic α-tocopherol concentrations during excess vitamin E administration remains unclear. We hypothesized that increased hepatic α-tocopherol would cause a marked xenobiotic response. Thus, we assessed cytochrome P450 oxidation systems (phase I), conjugation systems (phase II), and transporters (phase III) after daily α-tocopherol injections (100mg/kg body wt) for up to 9days in rats. α-Tocopherol injections increased hepatic α-tocopherol concentrations nearly 20-fold, along with a 10-fold increase in the hepatic α-tocopherol metabolites α-CEHC and α-CMBHC. Expression of phase I (CYP3A2, CYP3A1, CYP2B2) and phase II (SULT2A1) proteins and/or mRNA... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5273269 Sat, 03 Sep 2011 04:00:00 +0100 5273269 http://www.medworm.com/index.php?rid=5273271&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945097%26dopt%3DAbstract Authors: Aliche-Djoudi F, Podechard N, Chevanne M, Nourissat P, Catheline D, Legrand P, Dimanche-Boitrel MT, Lagadic-Gossmann D, Sergent O Abstract Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported to modulate lipid raft-dependent signaling, but not yet lipid raft-dependent oxidative stress. Previously, we have shown that ethanol-induced membrane remodeling, i.e., an increase in membrane fluidity and alterations in physical and biochemical properties of lipid rafts, participated in the development of oxidative stress. Thus, we decided to study n-3 PUFA effects in this context, by pretreating hepatocytes with eicosapentaenoic acid (EPA), a long-chain n-3 PUFA, before addition of ethanol. EPA was found to increase ethanol-induced oxidative stress through membrane... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5273271 Thu, 01 Sep 2011 04:00:00 +0100 5273271 http://www.medworm.com/index.php?rid=5273270&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945098%26dopt%3DAbstract Authors: Schneider L, Giordano S, Zelickson BR, Johnson M, Benavides G, Ouyang X, Fineberg N, Darley-Usmar VM, Zhang J Abstract Cell differentiation is associated with changes in metabolism and function. Understanding these changes during differentiation is important in the context of stem cell research, cancer, and neurodegenerative diseases. An early event in neurodegenerative diseases is the alteration of mitochondrial function and increased oxidative stress. Studies using both undifferentiated and differentiated SH-SY5Y neuroblastoma cells have shown distinct responses to cellular stressors; however, the mechanisms remain unclear. We hypothesized that because the regulation of glycolysis and oxidative phosphorylation is modulated during cellular differentiation, this would chan... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5273270 Thu, 01 Sep 2011 04:00:00 +0100 5273270 http://www.medworm.com/index.php?rid=5273268&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21946068%26dopt%3DAbstract This study investigated the mechanisms underlying aldosterone-induced increase in cell oxidants in kidney tubule cells. Aldosterone caused an increase in both reactive oxygen and reactive nitrogen (RNS) species. The involvement of the activation of NADPH oxidase in the increase in cellular oxidants was demonstrated by the inhibitory action of the NADPH oxidase inhibitors DPI, apocynin, and VAS2870 and by the migration of the p47 subunit to the membrane. NADPH oxidase activation occurred as a consequence of an increase in cellular calcium levels and was mediated by protein kinase C. The prevention of RNS increase by BAPTA-AM, W-7, and L-NAME indicates a calcium-calmodulin activation of NOS. A similar pattern of effects of the NADPH oxidase and NOS inhibitors was observed for aldosterone-ind... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5273268 Thu, 01 Sep 2011 04:00:00 +0100 5273268 http://www.medworm.com/index.php?rid=5241041&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21930200%26dopt%3DAbstract In this study, we sought to characterize the oxidative modification of LDL that is responsible for this prosurvival effect. We found that both the modified lipid and the modified protein components of oxLDL can increase the viability of macrophages. The key modification appeared to involve derivatization of amino groups in apoB or in phosphatidylethanolamine by lipid peroxidation products. These reactive oxidation products were primarily unfragmented hydroperoxide- or endoperoxide-containing oxidation products of linoleic acid or arachidonic acid. LC-MS/MS studies showed that some of the arachidonic acid-derived lysine adducts were isolevuglandins that contain lactam and hydroxylactam rings. MS/MS analysis of linoleic acid autoxidation adducts was consistent with 5- or 6-membered nitrogen-... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5241041 Thu, 01 Sep 2011 04:00:00 +0100 5241041 http://www.medworm.com/index.php?rid=5241045&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925591%26dopt%3DAbstract Authors: Kim Y, Kim BH, Lee H, Jeon B, Lee YS, Kwon MJ, Kim TY Abstract Extracellular superoxide dismutase (EC-SOD) is an antioxidant enzyme that breaks down superoxide anion into oxygen and hydrogen peroxide in extracellular spaces and plays key roles in controlling pulmonary and vascular diseases in response to oxidative stresses. We aimed to investigate the role of EC-SOD in angiogenesis and inflammation in chronic inflammatory skin disorders such as psoriasis. Overexpressed EC-SOD reduced expression of angiogenic factors and proinflammatory mediators in hypoxia-induced keratinocytes and in ultraviolet B-irradiated mice, whereas the expression of the antiangiogenic factor tissue inhibitor of metalloproteinase-1 and anti-inflammatory cytokine interleukin-10 were increased. EC-SOD... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5241045 Tue, 30 Aug 2011 04:00:00 +0100 5241045 http://www.medworm.com/index.php?rid=5241044&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925593%26dopt%3DAbstract Response to "A critical evaluation of cpYFP as a probe for superoxide" Free Radic Biol Med. 2011 Aug 30; Authors: Huang Z, Zhang W, Gong G, Fang H, Zheng M, Wang X, Xu J, Dirksen RT, Sheu SS, Cheng H, Wang W PMID: 21925593 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine) Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5241044 Tue, 30 Aug 2011 04:00:00 +0100 5241044 http://www.medworm.com/index.php?rid=5241043&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925594%26dopt%3DAbstract Authors: Gladden JD, Zelickson BR, Wei CC, Ulasova E, Zheng J, Ahmed MI, Chen Y, Bamman M, Ballinger S, Darley-Usmar V, Dell'italia LJ Abstract Xanthine oxidoreductase (XOR) is increased in the left ventricle (LV) of humans with volume overload (VO), and mitochondrial inhibition of the respiratory chain occurs in animal models of VO. Because mitochondria are both a source and a target of reactive oxygen and nitrogen species, we hypothesized that activation of XOR and mitochondrial dysfunction are interdependent. To test this we used the aortocaval fistula (ACF) rat model of VO and a simulation of the stretch response in isolated adult cardiomyocytes with and without the inhibitor of XOR, allopurinol, or the mitochondrially targeted antioxidant MitoQ. Xanthine oxidase (XO) activity ... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5241043 Tue, 30 Aug 2011 04:00:00 +0100 5241043 http://www.medworm.com/index.php?rid=5241042&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925595%26dopt%3DAbstract This study reveals the opposite roles of HIF-1α and HIF-2α in the regulation of IL-8 expression in endothelial cells. However, despite stabilization of both isoforms in hypoxia the effect of HIF-1 is predominant, and downregulation of IL-8 expression in hypoxia is caused by attenuation of Nrf2 and c-Myc. PMID: 21925595 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine) Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5241042 Tue, 30 Aug 2011 04:00:00 +0100 5241042 http://www.medworm.com/index.php?rid=5225845&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920432%26dopt%3DAbstract This study explores the toxicity mechanism of ZnO and TiO(2) ENPs in a gram-negative bacterium, Escherichia coli. Internalization and uniform distribution of characterized bare ENPs in the nano range without agglomeration was observed in E. coli by electron microscopy and flow cytometry. Our data showed a statistically significant concentration-dependent decrease in E. coli cell viability by both conventional plate count method and flow cytometric live-dead discrimination assay. Significant (p<0.05) DNA damage in E. coli cells was also observed after ENP treatment. Glutathione depletion with a concomitant increase in hydroperoxide ions, malondialdehyde levels, reactive oxygen species, and lactate dehydrogenase activity demonstrates that ZnO and TiO(2) ENPs induce oxidative stress leadin... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5225845 Sun, 28 Aug 2011 04:00:00 +0100 5225845 http://www.medworm.com/index.php?rid=5225846&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21914470%26dopt%3DAbstract Authors: Ghosh S, Dungdung SR, Chowdhury ST, Mandal AK, Sarkar S, Ghosh D, Das N Abstract Chronic arsenic exposure causes oxidative stress and mitochondrial dysfunction in the liver and brain. The ideal treatment would be to chelate arsenic and prevent oxidative stress. meso-2,3-Dimercaptosuccinic acid (DMSA) is used to chelate arsenic but its hydrophilicity makes it membrane-impermeative. Conversely, quercetin (QC) is a good antioxidant with limited clinical application because of its hydrophobic nature and limited bioavailability, and it is not possible to solubilize these two compounds in a single nontoxic solvent. Nanocapsules have emerged as a potent drug delivery system and make it feasible to incorporate both hydrophilic and lipophilic compounds. Nanoencapsulated formulation... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5225846 Fri, 26 Aug 2011 04:00:00 +0100 5225846 http://www.medworm.com/index.php?rid=5225844&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920433%26dopt%3DAbstract Authors: Inturi S, Tewari-Singh N, Gu M, Shrotriya S, Gomez J, Agarwal C, White CW, Agarwal R Abstract Employing mouse skin epidermal JB6 cells and dermal fibroblasts, here we examined the mechanisms of DNA damage by 2-chloroethyl ethyl sulfide (CEES), a monofunctional analog of sulfur mustard (SM). CEES exposure caused H2A.X and p53 phosphorylation as well as p53 accumulation in both cell types, starting at 1h, that was sustained for 24h, indicating a DNA-damaging effect of CEES, which was also confirmed and quantified by alkaline comet assay. CEES exposure also induced oxidative stress and oxidative DNA damage in both cell types, measured by an increase in mitochondrial and cellular reactive oxygen species and 8-hydroxydeoxyguanosine levels, respectively. In the studies distingui... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5225844 Fri, 26 Aug 2011 04:00:00 +0100 5225844 http://www.medworm.com/index.php?rid=5225847&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21911054%26dopt%3DAbstract Authors: Dos Santos JM, Tewari S, Goldberg AF, Kowluru RA Abstract Retinal mitochondria become dysfunctional and their DNA (mtDNA) is damaged in diabetes. The biogenesis of mitochondrial DNA is tightly controlled by nuclear-mitochondrial transcriptional factors, and translocation of transcription factor A (TFAM) to the mitochondria is essential for transcription and replication. Our aim is to investigate the effects of diabetes on nuclear-mitochondrial communication in the retina and its role in the development of retinopathy. Damage of mtDNA, copy number, and biogenesis (PGC1, NRF1, TFAM) were analyzed in the retinas from streptozotocin-diabetic wild-type (WT) and MnSOD transgenic (Tg) mice. Binding between TFAM and chaperone Hsp70 was quantified by coimmunoprecipitation. The key ... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5225847 Thu, 25 Aug 2011 04:00:00 +0100 5225847 http://www.medworm.com/index.php?rid=5215791&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21906672%26dopt%3DAbstract In this report, we observed that plasma levels of angiotensin II and catecholamines were increased in KAP Tg mice, compared with wild-type animals. Systemic administration of Tempol, a membrane-permeative superoxide dismutase mimetic, reduced arterial pressure as well as urinary excretion of oxidative stress markers and reduced both angiotensin II and norepinephrine plasma levels in KAP Tg mice. Intracerebroventricular administration of Tempol also reduced arterial pressure in Tg mice. Moreover, administration of apocynin and DPI, inhibitors of NADPH oxidase, a major source of ROS, also reduced arterial pressure and both angiotensin II and norepinephrine plasma levels in Tg mice. Thus, we analyzed the involvement of the RAS and sympathetic nervous system in KAP Tg mouse hypertension. Both ... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5215791 Thu, 25 Aug 2011 04:00:00 +0100 5215791 http://www.medworm.com/index.php?rid=5215787&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907278%26dopt%3DAbstract Authors: Ramanathan L, Siegel JM Abstract We previously showed that total sleep deprivation increased antioxidant responses in several rat brain regions. We also reported that chronic hypoxia enhanced antioxidant responses and increased oxidative stress in rat cerebellum and pons, relative to normoxic conditions. In the current study, we examined the interaction between these two parameters (sleep and hypoxia). We exposed rats to total sleep deprivation under sustained hypoxia (SDSH) and compared changes in antioxidant responses and oxidative stress markers in the neocortex, hippocampus, brain stem, and cerebellum to those in control animals left undisturbed under either sustained hypoxia (UCSH) or normoxia. We measured changes in total nitrite levels as an indicator of nitric oxid... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5215787 Thu, 25 Aug 2011 04:00:00 +0100 5215787 http://www.medworm.com/index.php?rid=5215786&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907790%26dopt%3DAbstract Authors: Asensio-López MC, Lax A, Pascual-Figal DA, Valdés M, Sánchez-Más J Abstract Doxorubicin has cardiotoxic effects that limit its clinical benefit in cancer patients. Metformin exerts cardioprotective actions via AMP-activated protein kinase (AMPK) and increases the expression of adiponectin and its receptors (adipoR1 and adipoR2) in skeletal muscle and adipose tissue, but its effect on cardiac tissue is still unknown. This work aimed to study whether metformin exerts any protective action against the cardiotoxicity of doxorubicin and whether the cardiac system of adiponectin is involved in any such action. The addition of doxorubicin (5μM) to adult mouse cardiomyocytes (HL-1 cell line) induced apoptosis, which was characterized by a loss of cell viability, activation of... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5215786 Thu, 25 Aug 2011 04:00:00 +0100 5215786 http://www.medworm.com/index.php?rid=5215792&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21906671%26dopt%3DAbstract In this study, we tested the hypothesis that omeprazole attenuates hyperoxia-induced cytotoxicity, ROS generation, and expression of monocyte chemoattractant protein-1 (MCP-1) in human lung-derived H441 cells via AhR activation. Experimental groups included cells transfected with AhR small interfering RNA (siRNA). Hyperoxia resulted in significant increases in cytotoxicity, ROS generation, and MCP-1 production, which were significantly attenuated with the functional activation of AhR by omeprazole. The protective effects of omeprazole on cytotoxicity, ROS production, and MCP-1 production were lost in H441 cells whose AhR gene was silenced by AhR siRNA. These findings support the hypothesis that omeprazole protects against hyperoxic injury in vitro via AhR activation that is associated with... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5215792 Tue, 23 Aug 2011 04:00:00 +0100 5215792 http://www.medworm.com/index.php?rid=5215790&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21906673%26dopt%3DAbstract Authors: Chen JL, Huang YJ, Pan CH, Hu CW, Chao MR Abstract A highly sensitive quantitative LC-MS/MS method was developed for measuring urinary malondialdehyde (MDA). With the use of an isotope internal standard and online solid-phase extraction, urine samples can be directly analyzed within 10min after 2,4-dinitrophenylhydrazine (DNPH) derivatization. The detection limit was estimated as 0.08pmol. This method was further applied to assess the optimal addition of DNPH for derivatization and to measure urinary MDA in 80 coke oven emission (COE)-exposed and 67 nonexposed workers. Derivatization optimization revealed that to achieve complete derivatization reaction, an excess of DNPH is required (DNPH/MDA molar ratio: 893/8929) for urine samples that is about 100 times higher than tha... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5215790 Tue, 23 Aug 2011 04:00:00 +0100 5215790 http://www.medworm.com/index.php?rid=5215788&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907277%26dopt%3DAbstract The objective of this work was to analyze the possible association between cyclooxygenase-2 (COX-2) and NADPH oxidases (NOX) in liver cells, in response to various proinflammatory and toxic insults. First, we observed that treatment of Chang liver (CHL) cells with various COX-2 inducers increased reactive oxygen species (ROS) production concomitant with GSH depletion, phorbol 12-myristate 13-acetate (PMA) being the most effective treatment. Moreover, early changes in the oxidative status induced by PMA were inhibited by glutathione ethyl ester, which also impeded COX-2 induction. In fact, CHL cells expressed NOX1 and NOX4, although only NOX4 expression was up-regulated in the presence of PMA. Knock-down experiments suggested that PMA initiated a pathway in which NOX1 activation controlled ... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5215788 Fri, 19 Aug 2011 04:00:00 +0100 5215788 http://www.medworm.com/index.php?rid=5215795&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21884783%26dopt%3DAbstract In this study it is shown that on exposure to MPO/H(2)O(2), thiols on plasma proteins from nonsmokers were increasingly oxidized with increasing added SCN(-) concentrations. Plasma from smokers contained significantly higher endogenous levels of SCN(-) than that from nonsmokers (131±31 vs 40±24μM, P<0.0001). When plasma from smokers and nonsmokers was exposed to MPO/H(2)O(2)-stimulated oxidation, a strong positive correlation (r=0.8139, P<0.0001) between the extent of thiol oxidation and the plasma SCN(-) concentrations was observed. Computational calculations indicate a changeover from HOCl to HOSCN as the major MPO-generated oxidant in plasma, with increasing SCN(-) levels. These data indicate that plasma SCN(-) levels are a key determinant of the extent of thiol oxidation on pl... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5215795 Thu, 18 Aug 2011 04:00:00 +0100 5215795 http://www.medworm.com/index.php?rid=5215793&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21893189%26dopt%3DAbstract This study aimed to elucidate the implications of mitochondrial oxidative stress on the immune pathophysiological mechanisms of OHCI. We herein report that OHCI induces mitochondrial oxidative stress, leading to DNA double-strand breaks and elicitation of a phosphoinositol 3-kinase-mediated cellular response in peripheral blood lymphocytes. Compared to controls, OHCI subjects showed higher accumulation of pATM, pATR, γH2AX, and p-p53, along with active recruitment of repair proteins (Mre11, Rad50, and Nbs1) and altered mitochondrial DNA content. Increased mitochondrial membrane depolarization and circulating nucleosome levels along with chromatid-type aberrations and decreased T-cell proliferative index observed in the OHCI group further indicated that this damage might lead to Bax-trigge... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5215793 Thu, 18 Aug 2011 04:00:00 +0100 5215793 http://www.medworm.com/index.php?rid=5215789&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21906674%26dopt%3DAbstract In this study, the effectiveness of the newly synthesized nitroxides 8-aza-7,7,9,9-tetramethyl-1,4-dioxaspiro[4.5]undecan-8-oxyl (compound 1) and 4-oxo-2,2,6,6-tetraethylpiperidine-1-oxyl (compound 2) in the prevention of gastric ulcers in adjuvant arthritis rats treated with indomethacin was evaluated by monitoring the reaction of reactive oxygen species in gastric tissue with Overhauser-enhanced magnetic resonance imaging (OMRI). Pretreatment with all tested nitroxides suppressed the ulcers induced by indomethacin treatment in arthritic rats. OMRI using compounds 1 and 2 as well as 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) demonstrated a redox imbalance in the stomach of these rats. Lipid peroxide and interleukin (IL)-1β levels in the gastric mucosa were significantly supp... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5215789 Thu, 18 Aug 2011 04:00:00 +0100 5215789 http://www.medworm.com/index.php?rid=5215796&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21875664%26dopt%3DAbstract Authors: Pupo E, Fiorio Pla A, Avanzato D, Moccia F, Avelino Cruz JE, Tanzi F, Merlino A, Mancardi D, Munaron L Abstract Hydrogen sulfide (H(2)S) is a gasotransmitter that plays several roles in various tissues, including the cardiovascular system. Because it has been recently proposed to act as a mediator of angiogenesis progression, here we investigate the effects of H(2)S in a well-established model of tumor angiogenesis: endothelial cells obtained from human breast carcinoma (B-TECs). Ca(2+) imaging and patch-clamp experiments reveal that acute perfusion with NaHS, a widely employed H(2)S donor, activates cytosolic calcium (Ca(c)) increase, as well as potassium and nonselective cationic currents, in B-TECs. Stimulation with NaHS in the same concentration range (1nM-200μM) evok... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5215796 Wed, 17 Aug 2011 04:00:00 +0100 5215796 http://www.medworm.com/index.php?rid=5215794&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21884784%26dopt%3DAbstract In this study, using a well-established model of nephropathy, we have explored the role of PARP-1 in cisplatin-induced kidney injury. Genetic deletion or pharmacological inhibition of PARP-1 markedly attenuated the cisplatin-induced histopathological damage, impaired renal function (elevated serum BUN and creatinine levels), and enhanced inflammatory response (leukocyte infiltration; TNF-α, IL-1β, F4/80, adhesion molecules ICAM-1/VCAM-1 expression) and consequent oxidative/nitrative stress (4-HNE, 8-OHdG, and nitrotyrosine content; NOX2/NOX4 expression). PARP inhibition also facilitated the cisplatin-induced death of cancer cells. Thus, PARP activation plays an important role in cisplatin-induced kidney injury, and its pharmacological inhibition may represent a promising approach to prev... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5215794 Wed, 17 Aug 2011 04:00:00 +0100 5215794 http://www.medworm.com/index.php?rid=5215797&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21872656%26dopt%3DAbstract Authors: Dranka BP, Benavides GA, Diers AR, Giordano S, Zelickson BR, Reily C, Zou L, Chatham JC, Hill BG, Zhang J, Landar A, Darley-Usmar VM Abstract It is now clear that mitochondria are an important target for oxidative stress in a broad range of pathologies, including cardiovascular disease, diabetes, neurodegeneration, and cancer. Methods for assessing the impact of reactive species on isolated mitochondria are well established but constrained by the need for large amounts of material to prepare intact mitochondria for polarographic measurements. With the availability of high-resolution polarography and fluorescence techniques for the measurement of oxygen concentration in solution, measurements of mitochondrial function in intact cells can be made. Recently, the development o... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5215797 Tue, 16 Aug 2011 04:00:00 +0100 5215797 http://www.medworm.com/index.php?rid=5215801&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21871559%26dopt%3DAbstract Authors: Langston JW, Li W, Harrison L, Aw TY Abstract Our recent finding that insulin increased the expression of the glutamate-cysteine ligase catalytic subunit (GCLc) with coincident increases in GCL activity and cellular glutathione (GSH) in human brain microvascular endothelial cells (IHECs) suggests a role for insulin in vascular GSH maintenance. Here, using IHECs stably transfected with promoter-luciferase reporter vectors, we found that insulin increased GCLc promoter activity, which required a prerequisite increase or decrease in medium glucose. An intact antioxidant response element-4 was essential for promoter activation, which was attenuated by inhibitors of PI3-kinase/Akt/mTOR signaling. Interestingly, only under low-glucose conditions did promoter activation correlate... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5215801 Fri, 12 Aug 2011 04:00:00 +0100 5215801 http://www.medworm.com/index.php?rid=5215800&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21871560%26dopt%3DAbstract We examined if FXa regulates PAR-1 and PAR-2 in human vascular SMCs. FXa increased PAR-2 mRNA, protein, and cell-surface expression and augmented PAR-2-mediated mitogenesis. PAR-1 was not influenced. The regulatory action of FXa on PAR-2 was concentration-dependent and mimicked by a PAR-2-selective activating peptide. PAR-2 regulation was not influenced by the thrombin inhibitor argatroban or PAR-1 siRNA. FXa increased dichlorofluorescein diacetate fluorescence and 8-isoprostane formation and induced expression of the NADPH oxidase subunit NOX-1. NOX-1 siRNA prevented FXa-stimulated PAR-2 regulation, as did ebselen and cell-permeative and impermeative forms of catalase. Exogenous H(2)O(2) increased PAR-2 expression and mitogenic activity. FXa promoted nuclear translocation and PAR-2/DNA bi... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5215800 Fri, 12 Aug 2011 04:00:00 +0100 5215800 http://www.medworm.com/index.php?rid=5215799&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21871561%26dopt%3DAbstract This study was designed to evaluate the effect of ALDH2 on ethanol-induced myocardial damage with a focus on autophagy. Wild-type FVB and transgenic mice overexpressing ALDH2 were challenged with ethanol (3g/kg/day, ip) for 3days and cardiac mechanical function was assessed using the echocardiographic and IonOptix systems. Western blot analysis was used to evaluate essential autophagy markers, Akt and AMPK, and the downstream signal mTOR. Ethanol challenge altered cardiac geometry and function as evidenced by enlarged ventricular end systolic and diastolic diameters, decreased cell shortening and intracellular Ca(2+) rise, prolonged relengthening and intracellular Ca(2+) decay, as well as reduced SERCA Ca(2+) uptake, which effects were mitigated by ALDH2. Ethanol challenge facilitated myoc... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5215799 Wed, 10 Aug 2011 04:00:00 +0100 5215799 http://www.medworm.com/index.php?rid=5215798&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21871954%26dopt%3DAbstract In this study we demonstrate that aging induces alterations in the activity and expression of principal components of the UPP. Additionally, we show that multiple changes in the UPP occur during the differentiation of 3T3-L1 cells into adipocytes. In vitro data link observed UPP alterations to increased levels of oxidative stress and altered adipose biology relevant to both aging and differentiation. Taken together, these data demonstrate that changes in the UPP occur in response to adipose aging and adipogenesis and strongly suggest that proteasome inhibition is sufficient to decrease adipose differentiation, as well as increasing oxidative stress in mature adipocytes, both of which probably promote deleterious effects on adipose aging. PMID: 21871954 [PubMed - as supplied by publishe... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5215798 Wed, 10 Aug 2011 04:00:00 +0100 5215798 http://www.medworm.com/index.php?rid=5171313&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21867749%26dopt%3DAbstract Authors: Was H, Sokolowska M, Sierpniowska A, Dominik P, Skrzypek K, Lackowska B, Pratnicki A, Grochot-Przeczek A, Taha H, Kotlinowski J, Kozakowska M, Mazan A, Nowak W, Muchova L, Vitek L, Ratajska A, Dulak J, Jozkowicz A Abstract Heme oxygenase-1 (HO-1) is an antioxidative and cytoprotective enzyme, which may protect neoplastic cells against anticancer therapies, thereby promoting the progression of growing tumors. Our aim was to investigate the role of HO-1 in cancer induction. Experiments were performed in HO-1(+/+), HO-1(+/-), and HO-1(-/-) mice subjected to chemical induction of squamous cell carcinoma with 7,12-dimethylbenz[a]anthracene and phorbol 12-myristate 13-acetate. Measurements of cytoprotective genes in the livers evidenced systemic oxidative stress in the mice of a... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5171313 Tue, 09 Aug 2011 23:00:00 +0100 5171313 http://www.medworm.com/index.php?rid=5171316&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21854842%26dopt%3DAbstract In conclusion, CaMKII and mitochondria confer oxidative stress-induced pathological cellular memory that leads to cardiac arrhythmia. PMID: 21854842 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine) Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5171316 Thu, 04 Aug 2011 23:00:00 +0100 5171316 http://www.medworm.com/index.php?rid=5171315&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21855628%26dopt%3DAbstract Authors: Cota-Gomez A, Flores AC, Ling X, Varella-Garcia M, Flores SC Abstract Chronic human immunodeficiency virus infection is associated with higher incidence of pulmonary complications including hypertension, vasculopathy, lymphocytic alveolitis, and interstitial pneumonitis not attributed to either opportunistic infections or presence of the virus. The Tat (transactivator of transcription) protein, a required transactivator for expression of full-length viral genes, is pleiotropic and influences expression of cellular inflammatory genes. Tat-dependent transactivation of cellular genes requires specific mediators, including NF-κB, widely recognized as sensitive to changes in cellular oxidant burden. We hypothesized that overproduction of Tat leads to increased oxidant burden a... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5171315 Thu, 04 Aug 2011 23:00:00 +0100 5171315 http://www.medworm.com/index.php?rid=5171314&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21856412%26dopt%3DAbstract Authors: Shoeb M, Yadav UC, Srivastava SK, Ramana KV Abstract The bacterial endotoxin lipopolysaccharide (LPS) is known to induce release of arachidonic acid (AA) and its metabolic products, which play important roles in the inflammatory process. We have shown earlier that LPS-induced signals in macrophages are mediated by aldose reductase (AR). Here we have investigated the role of AR in LPS-induced release of AA metabolites and their modulation using a potent pharmacological inhibitor, fidarestat, and AR siRNA ablation in RAW264.7 macrophages and AR-knockout mouse peritoneal macrophages and heart tissue. Inhibition or genetic ablation of AR prevented the LPS-induced synthesis and release of AA metabolites such as PGE2, TXB, PGI2, and LTBs in macrophages. LPS-induced activation of... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5171314 Thu, 04 Aug 2011 23:00:00 +0100 5171314 http://www.medworm.com/index.php?rid=5147444&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843633%26dopt%3DAbstract Authors: Crouzin N, Ferreira MC, Cohen-Solal C, M'kadmi C, Bernad N, Martinez J, Barbanel G, Vignes M, Guiramand J α-Tocopherol (α-TOH), a dietary component of vitamin E, is well known for its antioxidant capacity. Nevertheless, recent studies have pointed out non-anti-radical properties including cellular and genomic actions. Decreased levels of α-tocopherol in the brain are associated with neuronal dysfunctions ranging from mood disorders to neurodegeneration. All these behavioral effects of α-tocopherol deficiency probably do not rely simply on its anti-radical properties, but could also be reminiscent of a not-yet characterized neuromodulatory action. We have thus measured the direct actions of α-tocopherol and of its natural phosphate derivative, α-tocopheryl phosphate (α-T... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5147444 Wed, 03 Aug 2011 23:00:00 +0100 5147444 http://www.medworm.com/index.php?rid=5147446&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839827%26dopt%3DAbstract Authors: Cabreiro F, Ackerman D, Doonan R, Araiz C, Back P, Papp D, Braeckman BP, Gems D The superoxide free radical (O(2)(•-)) has been viewed as a likely major contributor to aging. If this is correct, then superoxide dismutase (SOD), which removes O(2)(•-), should contribute to longevity assurance. In Caenorhabditis elegans, overexpression (OE) of the major cytosolic Cu/Zn-SOD, sod-1, increases life span. But is this increase caused by enhanced antioxidant defense? sod-1 OE did not reduce measures of lipid oxidation or glycation and actually increased levels of protein oxidation. The effect of sod-1 OE on life span was dependent on the DAF-16/FoxO transcription factor (TF) and, partially, on the heat shock TF HSF-1. Similarly, overexpression of sod-2 (major mitochondrial Mn-SOD)... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5147446 Sat, 30 Jul 2011 23:00:00 +0100 5147446 http://www.medworm.com/index.php?rid=5147443&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843634%26dopt%3DAbstract In conclusion, we demonstrate that Hg(2+) regulates the expression of the NQO1 gene through a transcriptional mechanism in human hepatoma HepG2 cells. In addition, Nrf2 is involved in the modulation of NQO1 by Hg(2+). PMID: 21843634 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine) Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5147443 Sat, 30 Jul 2011 23:00:00 +0100 5147443 http://www.medworm.com/index.php?rid=5147450&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21827848%26dopt%3DAbstract Authors: Hebert-Schuster M, Cottart CH, Laguillier-Morizot C, Raynaud-Simon A, Golmard JL, Cynober L, Beaudeux JL, Fabre EE, Nivet-Antoine V Impaired glucose tolerance is common during aging. The transcription factor PAX6 is involved in glucose homeostasis. Computational promoter sequence analysis of the catalase gene highlighted a putative PAX6 binding site on the rs769214 polymorphism A allele. Creation of this binding site has been suggested to explain renutrition inefficiency in malnourished elderly patients. Our aim was to evaluate the link between the rs769214 polymorphism of the catalase gene and glucose homeostasis in malnourished elderly patients at inclusion and during renutrition. Thirty-three malnourished elderly Caucasian inpatients were recruited. Nutritional and inflamma... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5147450 Thu, 28 Jul 2011 23:00:00 +0100 5147450 http://www.medworm.com/index.php?rid=5147448&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839165%26dopt%3DAbstract In this study, the recombinant SOR from Giardia (SOR(Gi)) was purified and characterized by pulse radiolysis and stopped-flow spectrophotometry. The protein, isolated in the reduced state, after oxidation by superoxide or hexachloroiridate(IV), yields a resting species (T(final)) with Fe(3+) ligated to glutamate or hydroxide depending on pH (apparent pK(a)=8.7). Although showing negligible SOD activity, reduced SOR(Gi) reacts with O(2)(•-) with a pH-independent second-order rate constant k(1)=1.0×10(9)M(-1)s(-1) and yields the ferric-(hydro)peroxo intermediate T(1); this in turn rapidly decays to the T(final) state with pH-dependent rates, without populating other detectable intermediates. Immunoblotting assays show that SOR(Gi) is expressed in the disease-causing trophozoite of Giardia... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5147448 Thu, 28 Jul 2011 23:00:00 +0100 5147448 http://www.medworm.com/index.php?rid=5147447&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839166%26dopt%3DAbstract We report the role of mitochondria in the protective effects of curcumin, a well-known direct and indirect antioxidant, against the renal oxidant damage induced by the hexavalent chromium [Cr(VI)] compound potassium dichromate (K(2)Cr(2)O(7)) in rats. Curcumin was given daily by gavage using three different schemes: (1) complete treatment (100, 200, and 400mg/kg bw 10days before and 2days after K(2)Cr(2)O(7) injection), (2) pretreatment (400mg/kg bw for 10days before K(2)Cr(2)O(7) injection), and (3) posttreatment (400mg/kg bw 2days after K(2)Cr(2)O(7) injection). Rats were sacrificed 48h later after a single K(2)Cr(2)O(7) injection (15mg/kg, sc) to evaluate renal and mitochondrial function and oxidant stress. Curcumin treatment (schemes 1 and 2) attenuated K(2)Cr(2)O(7)-induced renal dysf... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5147447 Thu, 28 Jul 2011 23:00:00 +0100 5147447 http://www.medworm.com/index.php?rid=5147445&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843632%26dopt%3DAbstract Authors: Park L, Min D, Kim H, Chung HY, Lee CH, Park IS, Kim Y, Park Y Metallothioneins (MTs) are intracellular low-molecular-weight, cysteine-rich proteins with potent metal-binding and redox functions, but with limited membrane permeativity. The aim of this study was to investigate whether we could enhance delivery of MT-1 to pancreatic islets or β cells in vitro and in vivo. The second goal was to determine whether increased MT-1 could prevent cellular toxicity induced by high glucose and free fatty acids in vitro (glucolipotoxicity) and ameliorate the development of diabetes induced by streptozotocin in mice or delay the development of diabetes by improving insulin secretion and resistance in the OLETF rat model of type 2 diabetes. Expression of HIV-1 Tat-MT-1 enabled efficient d... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5147445 Thu, 28 Jul 2011 23:00:00 +0100 5147445 http://www.medworm.com/index.php?rid=5147457&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21820046%26dopt%3DAbstract The objective of this review is to provide an overview regarding the relationship between oxidative stress and AR signaling in the context of PCa and especially CRPC. Additionally, we discuss the potential use of antioxidant therapies in the treatment of PCa. PMID: 21820046 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine) Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5147457 Fri, 22 Jul 2011 23:00:00 +0100 5147457 http://www.medworm.com/index.php?rid=5147453&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21821119%26dopt%3DAbstract Authors: Veniamin S, Sawatzky LG, Banting GS, Glerum DM A number of distinct cuproproteins of the mitochondrial inner membrane are required for the assembly of cytochrome oxidase (COX), thought to function in a "bucket brigade" fashion to provide copper to the Cu(A) and Cu(B) sites. In yeast, the loss of two these proteins, Sco1p and Cox11p, leads to respiratory deficiency and a specific inability to survive exposure to hydrogen peroxide (H(2)O(2)). Using a quantitative assay, we have identified subtle differences in the peroxide-sensitive phenotypes between sco1 and cox11 mutant strains. Interestingly, the peroxide sensitivity of the sco1 null strain can be suppressed by overexpressing either SCO2 or COX11, although overexpression of neither SCO1 nor SCO2 can rescue the cox11 null str... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5147453 Fri, 22 Jul 2011 23:00:00 +0100 5147453 http://www.medworm.com/index.php?rid=5147452&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21824515%26dopt%3DAbstract Authors: Obolensky A, Berenshtein E, Lederman M, Bulvik B, Alper-Pinus R, Yaul R, Deleon E, Chowers I, Chevion M, Banin E Iron-associated oxidative injury plays a role in retinal degeneration such as age-related macular degeneration and retinitis pigmentosa. The metallo-complex zinc-desferrioxamine (Zn/DFO) may ameliorate such injury by chelation of labile iron in combination with release of zinc. We explored whether Zn/DFO can affect the course of retinal degeneration in the rd10 mouse model of retinitis pigmentosa. Zn/DFO-treated animals showed significantly higher electroretinographic responses at 3 and 4.5weeks of age compared with saline-injected controls. Corresponding retinal (photoreceptor) structural rescue was observed by quantitative histological and immunohistochemical tech... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5147452 Fri, 22 Jul 2011 23:00:00 +0100 5147452 http://www.medworm.com/index.php?rid=5147449&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21835240%26dopt%3DAbstract Authors: Denamur S, Tyteca D, Marchand-Brynaert J, Van Bambeke F, Tulkens PM, Courtoy PJ, Mingeot-Leclercq MP Gentamicin, an aminoglycoside antibiotic used to treat severe bacterial infections, may cause acute renal failure. At therapeutic concentrations, gentamicin accumulates in lysosomes and induces apoptosis in kidney proximal tubular cells. In gentamicin-treated renal LLC-PK1 cells, acridine orange release from lysosomes, previously interpreted as lysosomal membrane permeabilization, precedes the apoptotic cascade that develops during incubation with gentamicin. However, the link between gentamicin lysosomal accumulation and apoptosis remains unclear. We here examined if reactive oxygen species (ROS) production could account for gentamicin-induced acridine orange release and apopt... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5147449 Fri, 22 Jul 2011 23:00:00 +0100 5147449 http://www.medworm.com/index.php?rid=5147451&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21824516%26dopt%3DAbstract The objective of this study was to determine whether exposing rats to ozone would result in the loss of antioxidants from plasma and bronchoalveolar lavage fluid (BALF). Additional goals were to compare analyses of the same antioxidant concentration between different laboratories, to investigate which methods have the sensitivity to detect decreased levels of antioxidants, and to identify a reliable measure of oxidative stress in ozone-exposed rats. Male Fisher rats were exposed to either 2.0 or 5.0ppm ozone inhalation for 2h. Blood plasma and BALF samples were collected 2, 7, and 16h after the exposure. It was found that ascorbic acid in plasma collected from rats after the higher dose of ozone was lower at 2h but not later. BALF concentrations of ascorbic acid were decreased at both 2 an... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5147451 Thu, 21 Jul 2011 23:00:00 +0100 5147451 http://www.medworm.com/index.php?rid=5147459&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21816219%26dopt%3DAbstract Authors: Cerqueira FM, da Cunha FM, Caldeira da Silva CC, Chausse B, Romano RL, Garcia CC, Colepicolo P, Medeiros MH, Kowaltowski AJ Calorie restriction is a dietary intervention known to improve redox state, glucose tolerance, and animal life span. Other interventions have been adopted as study models for caloric restriction, including nonsupplemented food restriction and intermittent, every-other-day feedings. We compared the short- and long-term effects of these interventions to ad libitum protocols and found that, although all restricted diets decrease body weight, intermittent feeding did not decrease intra-abdominal adiposity. Short-term calorie restriction and intermittent feeding presented similar results relative to glucose tolerance. Surprisingly, long-term intermittent feedi... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5147459 Wed, 20 Jul 2011 23:00:00 +0100 5147459 http://www.medworm.com/index.php?rid=5147460&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21810465%26dopt%3DAbstract Authors: Tang H, Viola HM, Filipovska A, Hool LC Glutathionylation as a posttranslational modification of proteins is becoming increasingly recognized, but its role in many diseases has not been demonstrated. Oxidative stress and alterations in calcium homeostasis are associated with the development of cardiac hypertrophy. Because the cardiac L-type Ca(2+) channel can be persistently activated after exposure to H(2)O(2), the aim of this study was to determine whether alterations in channel function were associated with glutathionylation of the α(1C) subunit (Ca(v)1.2) channel protein. Immunoblot analysis indicated that Ca(v)1.2 protein is significantly glutathionylated after exposure to H(2)O(2) and glutathione in vitro and after ischemia-reperfusion injury. L-type Ca(2+) channel macr... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5147460 Mon, 18 Jul 2011 23:00:00 +0100 5147460 http://www.medworm.com/index.php?rid=5147458&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21816220%26dopt%3DAbstract In conclusion, we demonstrated that increased Nrf2 activity resulted in a reduction in HNE sensitivity in prostate cancer cells, suggesting a potential mechanism of resistance to pro-oxidant therapy. PMID: 21816220 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine) Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5147458 Mon, 18 Jul 2011 23:00:00 +0100 5147458 http://www.medworm.com/index.php?rid=5147456&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21820047%26dopt%3DAbstract Authors: Broedbaek K, Weimann A, Stovgaard ES, Poulsen HE The increasing prevalence of diabetes together with the associated morbidity and mortality calls for additional preventive and therapeutic strategies. New biomarkers that can be used in therapy control and risk stratification as alternatives to current methods are needed and can facilitate a more individualized and sufficient treatment of diabetes. Evidence derived from both epidemiological and mechanistic studies suggests that oxidative stress has an important role in mediating the pathologies of diabetic complications. A marker of intracellular oxidative stress that potentially could be used as a valuable biomarker in diabetes is the DNA oxidation marker 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), which can be assessed noni... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5147456 Mon, 18 Jul 2011 23:00:00 +0100 5147456 http://www.medworm.com/index.php?rid=5147455&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21820048%26dopt%3DAbstract Authors: Bai YP, Hu CP, Yuan Q, Peng J, Shi RZ, Yang TL, Cao ZH, Li YJ, Cheng G, Zhang GG Myeloperoxidase (MPO) is an important enzyme involved in the genesis and development of atherosclerosis. Vascular peroxidase 1 (VPO1) is a newly discovered member of the peroxidase family that is mainly expressed in vascular endothelial cells and smooth muscle cells and has structural characteristics and biological activity similar to those of MPO. Our specific aims were to explore the effects of VPO1 on endothelial cell apoptosis induced by oxidized low-density lipoprotein (ox-LDL) and the underlying mechanisms. The results showed that ox-LDL induced endothelial cell apoptosis and the expression of VPO1 in endothelial cells in a concentration- and time-dependent manner concomitant with increased ... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5147455 Mon, 18 Jul 2011 23:00:00 +0100 5147455 http://www.medworm.com/index.php?rid=5147454&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21820506%26dopt%3DAbstract This study suggests that multiple redox signals generate gene-specific modules affecting their expression. PMID: 21820506 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine) Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5147454 Mon, 18 Jul 2011 23:00:00 +0100 5147454 http://www.medworm.com/index.php?rid=5090221&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21807091%26dopt%3DAbstract In this study, we have studied radicals formed from both soybean and human cellular (PC3-15LOS cells) 15-LOX-catalyzed peroxidation of DPAs at various pH's using a combination of LC/ESR/MS with the spin trapping technique. We observed a total of three carbon-centered radicals formed in 15-LOX-DPA (n-3) stemming from its 7-, 17-, and 20-hydroperoxides, whereas only one formed from 17-hydroperoxide in DPA (n-6). A change in the reaction pH from 8.5 (15-LOX enzyme optimum) to 7.4 (physiological) and to 6.5 (tumor, acidic) not only decreased the total radical formation but also altered the preferred site of oxygenation. This pH-dependent alteration of radical formation and oxygenation pattern may have significant implications and provide a basis for our ongoing investigations of LOXs as well a... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5090221 Mon, 18 Jul 2011 23:00:00 +0100 5090221 http://www.medworm.com/index.php?rid=5090234&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21801832%26dopt%3DAbstract Authors: Qin CX, Williams SJ, Woodman OL The mechanism of flavonol-induced cardioprotection is unclear. We compared the protective actions of a flavonol that inhibits calcium utilization and has antioxidant activity, 3',4'-dihydroxyflavonol (DiOHF); a flavonol that affects only calcium activity, 4'-OH-3'-OCH(3)-flavonol (4'-OH-3'-OCH(3)F); and a water-soluble flavonol with selective antioxidant activity, DiOHF-6-succinamic acid (DiOHF-6-SA), in isolated, perfused rat hearts. Hearts were subjected to global ischemia for 20min followed by 30min reperfusion and were treated with vehicle (0.05% DMSO), DiOHF, 4'-OH-3'-OCH(3)F, or DiOHF-6-SA (all 10μM, n=6-8 per group). Flavonols were infused for 10min before ischemia and during reperfusion. In vehicle-treated hearts, left-ventricular (LV) ... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5090234 Sun, 17 Jul 2011 23:00:00 +0100 5090234 http://www.medworm.com/index.php?rid=5090237&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21798344%26dopt%3DAbstract Authors: Cheng G, Li H, Cao Z, Qiu X, McCormick S, Thannickal VJ, Nauseef WM Members of the peroxidase-cyclooxygenase superfamily catalyze biochemical reactions essential to a broad spectrum of biological processes, including host defense, thyroid hormone biosynthesis, and modification of extracellular matrix, as well as contributing to the pathogenesis of chronic inflammatory diseases. We recently identified a novel member of this family, vascular peroxidase-1 (VPO1), that is highly expressed in the human cardiovascular system. Its biosynthesis and enzymatic properties are largely unknown. Here, we report that VPO1 was rapidly and efficiently secreted into the extracellular space when the gene was stably expressed in human embryonic kidney (HEK) cells. Secreted VPO1 is a monomer with ... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5090237 Mon, 11 Jul 2011 23:00:00 +0100 5090237 http://www.medworm.com/index.php?rid=5090232&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21802509%26dopt%3DAbstract Authors: Czerniczyniec A, Karadayian AG, Bustamante J, Cutrera RA, Lores Arnaiz S Paraquat is a highly toxic quaternary nitrogen herbicide capable of increasing superoxide anion production. The aim of this research was to evaluate various behavioral changes and study cortical, hippocampal, and striatal mitochondrial function in an experimental model of paraquat toxicity in rats. Paraquat (10mg/kg ip) was administered weekly for a month. Anxiety-like behavior was evidenced in the paraquat-treated group as shown by a diminished time spent in, and fewer entries into, the open arms of an elevated-plus maze. Also, paraquat treatment induced a deficit in the sense of smell. In biochemical assays, NADH-cytochrome c reductase activity was significantly inhibited by 25 and 34% in cortical and s... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5090232 Mon, 11 Jul 2011 23:00:00 +0100 5090232 http://www.medworm.com/index.php?rid=5039547&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21742028%26dopt%3DAbstract Authors: Kar S, Kavdia M Endothelial dysfunction is associated with increase in oxidative stress and low NO bioavailability. The endothelial NO synthase (eNOS) uncoupling is considered an important factor in endothelial cell oxidative stress. Under increased oxidative stress, the eNOS cofactor tetrahydrobiopterin (BH(4)) is oxidized to dihydrobiopterin, which competes with BH(4) for binding to eNOS, resulting in eNOS uncoupling and reduction in NO production. The importance of the ratio of BH(4) to oxidized biopterins versus absolute levels of total biopterin in determining the extent of eNOS uncoupling remains to be determined. We have developed a computational model to simulate the kinetics of the biochemical pathways of eNOS for both NO and O(2)(•-) production to understand the ro... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5039547 Wed, 06 Jul 2011 23:00:00 +0100 5039547 http://www.medworm.com/index.php?rid=5039540&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21767632%26dopt%3DAbstract Authors: Liang CJ, Wang SH, Chen YH, Chang SS, Hwang TL, Leu YL, Tseng YC, Li CY, Chen YL Viscolin, a major active component in a chloroform extract of Viscum coloratum, has antioxidative and anti-inflammatory properties. We focused on its effects on the expression of vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-α (TNF-α)-treated human umbilical vein endothelial cells (HUVECs). The TNF-α-induced expression of VCAM-1 was significantly reduced by respectively 38±7 or 34±16% when HUVECs were pretreated with 10 or 30μM viscolin, as shown by Western blotting, and was also significantly reduced by pretreatment with the antioxidants N-acetylcysteine, diphenylene iodonium chloride, and apocynin. Viscolin also reduced TNF-α-induced VCAM-1 mRNA expression and promot... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5039540 Tue, 05 Jul 2011 23:00:00 +0100 5039540 http://www.medworm.com/index.php?rid=5039551&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21736939%26dopt%3DAbstract Authors: Usui S, Oveson BC, Iwase T, Lu L, Lee SY, Jo YJ, Wu Z, Choi EY, Samulski RJ, Campochiaro PA In retinitis pigmentosa (RP), various mutations cause rod photoreceptor cell death leading to increased oxygen levels in the outer retina, progressive oxidative damage to cones, and gradual loss of cone cell function. We have been exploring the potential of overexpressing components of the endogenous antioxidant defense system to preserve cone cell function in rd10(+/+) mice, a model of RP. rd10(+/+) mice deficient in superoxide dismutase 1 (SOD1) showed increased levels of superoxide radicals and carbonyl adducts (a marker of oxidative damage) in the retina and more rapid loss of cone function than rd10(+/+) mice with normal levels of SOD1. This suggests that SOD1 is an important compo... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5039551 Sun, 03 Jul 2011 23:00:00 +0100 5039551 http://www.medworm.com/index.php?rid=5039554&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723387%26dopt%3DAbstract Authors: Valdez LB, Zaobornyj T, Bombicino S, Iglesias DE, Boveris A, Donato M, D'Annunzio V, Buchholz B, Gelpi RJ Isolated rabbit hearts were exposed to ischemia (I; 15min) and reperfusion (R; 5-30min) in a model of stunned myocardium. I/R decreased left-ventricle O(2) consumption (46%) and malate-glutamate-supported mitochondrial state 3 respiration (32%). Activity of complex I was 28% lower after I/R. The pattern observed for the decline in complex I activity was also observed for the reduction in mitochondrial nitric oxide synthase (mtNOS) biochemical (28%) and functional (50%) activities, in accordance with the reported physical and functional interactions between complex I and mtNOS. Malate-glutamate-supported state 4 H(2)O(2) production was increased by 78% after I/R. Rabbit hea... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5039554 Wed, 29 Jun 2011 23:00:00 +0100 5039554 http://www.medworm.com/index.php?rid=5039543&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763418%26dopt%3DAbstract In this study, the effects of bufalin isolated from a traditional Chinese medicine were evaluated and characterized in HT-29 and Caco-2 human colon cancer cells. Contrary to its well-documented apoptosis-promoting activity in other cancer cells, bufalin did not cause caspase-dependent cell death in colon cancer cells, as indicated by the absence of significant early apoptosis as well as poly(ADP-ribose) polymerase and caspase-3 cleavage. Instead, bufalin activated an autophagy pathway, as characterized by the accumulation of LC3-II and the stimulation of autophagic flux. The induction of autophagy by bufalin was linked to the generation of reactive oxygen species (ROS). ROS activated autophagy via the c-Jun NH(2)-terminal kinase (JNK). JNK activation increased expression of ATG5 and Beclin... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5039543 Tue, 28 Jun 2011 23:00:00 +0100 5039543 http://www.medworm.com/index.php?rid=5039541&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763420%26dopt%3DAbstract In conclusion, the γ-ray irradiation-induced release of extracellular ATP may, at least in part, contribute to the production of ROS via purinergic signaling, leading to promotion of intracellular antioxidants as an adaptive response to an oxidative stress. PMID: 21763420 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine) Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5039541 Tue, 28 Jun 2011 23:00:00 +0100 5039541 http://www.medworm.com/index.php?rid=5039544&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21762778%26dopt%3DAbstract Authors: Aesif SW, Kuipers I, van der Velden J, Tully JE, Guala AS, Anathy V, Sheely JI, Reynaert NL, Wouters EF, van der Vliet A, Janssen-Heininger YM The transcription factor nuclear factor κB (NF-κB) is a critical regulator of inflammation and immunity and is negatively regulated via S-glutathionylation. The inhibitory effect of S-glutathionylation is overcome by glutaredoxin-1 (Grx1), which under physiological conditions catalyzes deglutathionylation and enhances NF-κB activation. The mechanisms whereby expression of the Glrx1 gene is regulated remain unknown. Here we examined the role of NF-κB in regulating activation of Glrx1. Transgenic mice that express a doxycycline-inducible constitutively active version of inhibitory κB kinase-β (CA-IKKβ) demonstrate elevated expressi... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5039544 Sun, 26 Jun 2011 23:00:00 +0100 5039544 http://www.medworm.com/index.php?rid=5039542&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763419%26dopt%3DAbstract This study has shown, for the first time, that plasma IsoF levels associate with higher oxygen tension in a human model of reperfusion, and this effect is significantly attenuated by hemoglobin. PMID: 21763419 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine) Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5039542 Sun, 26 Jun 2011 23:00:00 +0100 5039542 http://www.medworm.com/index.php?rid=5039545&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21762777%26dopt%3DAbstract Authors: Mailloux RJ, Harper ME Reactive oxygen species (ROS), natural by-products of aerobic respiration, are important cell signaling molecules, which left unchecked can severely impair cellular functions and induce cell death. Hence, cells have developed a series of systems to keep ROS in the nontoxic range. Uncoupling proteins (UCPs) 1-3 are mitochondrial anion carrier proteins that are purported to play important roles in minimizing ROS emission from the electron transport chain. The function of UCP1 in this regard is highly contentious. However, UCPs 2 and 3 are generally thought to be activated by ROS or ROS by-products to induce proton leak, thus providing a negative feedback loop for mitochondrial ROS production. In our laboratory, we have not only confirmed that ROS activate ... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5039545 Thu, 23 Jun 2011 23:00:00 +0100 5039545 http://www.medworm.com/index.php?rid=5039539&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21767633%26dopt%3DAbstract We report an entirely new role for the HSP70 chaperone in dissociating 26S proteasome complexes (into free 20S proteasomes and bound 19S regulators), preserving 19S regulators, and reconstituting 26S proteasomes in the first 1-3h after mild oxidative stress. These responses, coupled with direct 20S proteasome activation by poly(ADP ribose) polymerase in the nucleus and by PA28αβ in the cytoplasm, instantly provide cells with increased capacity to degrade oxidatively damaged proteins and to survive the initial effects of stress exposure. Subsequent adaptive (hormetic) processes (3-24h after stress exposure), mediated by several signal transduction pathways and involving increased transcription/translation of 20S proteasomes, immunoproteasomes, and PA28αβ, abrogate the need for 26S prote... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5039539 Thu, 23 Jun 2011 23:00:00 +0100 5039539 http://www.medworm.com/index.php?rid=5039550&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21741473%26dopt%3DAbstract Authors: Ishisaka A, Ichikawa S, Sakakibara H, Piskula MK, Nakamura T, Kato Y, Ito M, Miyamoto KI, Tsuji A, Kawai Y, Terao J Quercetin is widely distributed in vegetables and herbs and has been suggested to act as a neuroprotective agent. Here, we demonstrate that quercetin can accumulate enough to exert biological activity in rat brain tissues. Homogenates of perfused rat brain without detectable hemoglobin contaminants were treated with β-glucuronidase/sulfatase and the released quercetin and its methylated form were analyzed using high-performance liquid chromatography (HPLC) with three different detection methods. Both quercetin and the methylated form were detected in the brain of quercetin-administered rats using HPLC-UV and HPLC with electrochemical detection and were further i... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5039550 Wed, 22 Jun 2011 23:00:00 +0100 5039550 http://www.medworm.com/index.php?rid=5039549&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21741474%26dopt%3DAbstract Authors: Cuperus R, van Kuilenburg AB, Leen R, Bras J, Caron HN, Tytgat GA To enhance the efficacy of fenretinide (4HPR)-induced reactive oxygen species (ROS) in neuroblastoma, 4HPR was combined with buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, in neuroblastoma cell lines and spheroids, the latter being a three-dimensional tumor model. 4HPR exposure (2.5-10μM, 24h) resulted in ROS induction (114-633%) and increased GSH levels (68-120%). A GSH depletion of 80% of basal levels was observed in the presence of BSO (25-100μM, 24h). The 4HPR-BSO combination resulted in slightly increased ROS levels (1.1- to 1.3-fold) accompanied by an increase in cytotoxicity (110-150%) compared to 4HPR treatment alone. A correlation was observed between the ROS-inducing capac... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5039549 Wed, 22 Jun 2011 23:00:00 +0100 5039549 http://www.medworm.com/index.php?rid=5039548&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21741475%26dopt%3DAbstract In this study, we investigated a novel hypothesis for the mechanism of silica particle-induced increase in cytokine production. We studied the role of iron in lipid peroxidation-dependent transcription of cytokines in macrophages by ground natural silica particles at low sublethal doses. Particle size, size distribution, surface area, and structure were determined using electron microscopy, nitrogen adsorption, and X-ray diffraction. Iron impurity concentrations before and after acid treatment were determined by energy-dispersive X-ray and inductively coupled plasma mass spectroscopy. At a low noncytotoxic dose (1μg/ml) of 2-μm silica, the presence of iron significantly increased superoxide (O(2)(•-)), lipid peroxidation, lipid raft disruption, and cytokine production in macrophages. T... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5039548 Wed, 22 Jun 2011 23:00:00 +0100 5039548 http://www.medworm.com/index.php?rid=5039546&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21745563%26dopt%3DAbstract In this study, it is shown that the potency of flavones acting as topoisomerase I inhibitors can be ranked according to their redox properties and their 3D structure. Linear correlations were observed between the topoisomerase I inhibition activity exerted by five flavones (chrysin, apigenin, kaempferol, fisetin, and quercetin) and experimental and theoretical redox parameters of F. Moreover, theoretical calculations of the dihedral angle O(1)-2-1'-2' in the flavone molecules indicate the importance of their structural and steric features in their potency as topoisomerase I inhibitors. It is suggested that the flavones might interact with the DNA-topoisomerase I complex after their oxidation into quinones via autoxidation, enzymatic oxidation, or reactions with reactive oxygen species. Our... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5039546 Wed, 22 Jun 2011 23:00:00 +0100 5039546 http://www.medworm.com/index.php?rid=5039552&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723941%26dopt%3DAbstract Authors: Shin-Kang S, Ramsauer VP, Lightner J, Chakraborty K, Stone W, Campbell S, Reddy SA, Krishnan K Tocotrienols are members of the vitamin E family but, unlike tocopherols, possess an unsaturated isoprenoid side chain that confers superior anti-cancer properties. The ability of tocotrienols to selectively inhibit the HMG-CoA reductase pathway through posttranslational degradation and to suppress the activity of transcription factor NF-κB could be the basis for some of these properties. Our studies indicate that γ- and δ-tocotrienols have potent antiproliferative activity in pancreatic cancer cells (Panc-28, MIA PaCa-2, Panc-1, and BxPC-3). Indeed both tocotrienols induced cell death (>50%) by the MTT cell viability assay in all four pancreatic cancer cell lines. We also exam... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5039552 Mon, 20 Jun 2011 23:00:00 +0100 5039552 http://www.medworm.com/index.php?rid=5039553&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723388%26dopt%3DAbstract Authors: Chiarelli-Neto O, Pavani C, S Ferreira A, Uchoa AF, Severino D, Baptista MS We have studied the spectroscopic properties of hair (white, blond, red, brown, and black) under illumination with visible light, giving special emphasis to the photoinduced generation of singlet oxygen ((1)O(2)). Irradiation of hair shafts (λ(ex)>400nm) changed their properties by degrading the melanin. Formation of C3 hydroperoxides in the melanin indol groups was proven by (1)H NMR. After 532-nm excitation, all hair shafts presented the characteristic (1)O(2) emission (λ(em)=1270nm), whose intensity varied inversely with the melanin content. (1)O(2) lifetime was also shown to vary with hair type, being five times shorter in black hair than in blond hair, indicating the role of melanin as a (1)O... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=5039553 Tue, 14 Jun 2011 23:00:00 +0100 5039553 http://www.medworm.com/index.php?rid=4997302&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21683783%26dopt%3DAbstract Authors: Vitturi DA, Patel RP Beyond an inert oxidation product of nitric oxide (NO) metabolism, current thinking posits a key role for nitrite as a mediator of NO signaling, especially during hypoxia. This concept has been discussed in the context of nitrite serving a role as an endogenous modulator of NO homeostasis, but also from a novel clinical perspective whereby nitrite therapy may replenish NO signaling and prevent ischemic tissue injury. Indeed, the relatively rapid translation of studies delineating mechanisms of action to ongoing and planned clinical trials has been critical in fuelling interest in nitrite biology, and several excellent reviews have been written on this topic. In this article we limit our discussions to current concepts and what we feel are questions that re... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=4997302 Tue, 14 Jun 2011 23:00:00 +0100 4997302 http://www.medworm.com/index.php?rid=4997291&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21718783%26dopt%3DAbstract Authors: Dyson A, Bryan NS, Fernandez BO, Garcia-Saura MF, Saijo F, Mongardon N, Rodriguez J, Singer M, Feelisch M Most studies examining the metabolic fate of NO during systemic inflammation have focused on measuring the quantitatively predominating, stable anions nitrite and nitrate within the circulation. However, these are not necessarily the NO-related products that govern NO metabolism and signaling in tissues. We assessed all major NO derivatives temporally in blood and vital organs during inflammation and explored their relationship to insult severity and redox status. Male rats receiving intraperitoneal endotoxin or vehicle were sacrificed for organ and blood sampling between 0 and 24h. Endotoxin induced transient and organ-specific changes in a variety of NO metabolites. Nitr... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=4997291 Mon, 13 Jun 2011 23:00:00 +0100 4997291 http://www.medworm.com/index.php?rid=4997294&cid=s_35577_62_f&fid=35577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21712085%26dopt%3DAbstract This study examines the mechanisms by which 2',5'-dihydroxychalcone (2',5'-DHC) induces an increase in cellular glutathione (GSH) levels using a cell line stably expressing a luciferase reporter gene driven by antioxidant-response elements (MCF-7/AREc32). The 2',5'-DHC-induced increase in cellular GSH levels was partially inhibited by the catalytic antioxidant MnTDE-1,3-IP(5+), suggesting that reactive oxygen species (ROS) mediate the antioxidant adaptive response. 2',5'-DHC treatment induced phosphorylation of the c-Jun N-terminal kinase (JNK) pathway, which was also inhibited by MnTDE-1,3-IP(5+). These findings suggest a ROS-dependent activation of the AP-1 transcriptional response. However, whereas 2',5'-DHC triggered the NF-E2-related factor 2 (Nrf2) transcriptional response, cotreatme... Free Radical Biology and Medicine journals http://www.medworm.com/rss/comments.php?id=4997294 Sun, 12 Jun 2011 23:00:00 +0100 4997294