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Loss of Nrf2 markedly exacerbates non-alcoholic steatohepatitis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Non-alcoholic steatohepatitis (NASH) arises from non-alcoholic fatty liver disease (NAFLD) as a consequence of oxidative stress. Herein we report that the development of NASH is greatly accelerated in mice lacking transcription factor Nrf2 when they are challenged with a methionine- and choline-deficient (MCD) diet. Following 14-days feeding on an MCD diet, livers from Nrf2(-/-) mice showed a substantial increase in macro- and micro-vesicular steatosis and a massive increase in the number of neutrophil polymorphs, when compared to livers from wild-type mice treated similarly. Livers of Nrf2(-/-) mice on the MCD diet su...
Source: Free Radical Biology and Medicine - November 12, 2009 Category: Biology Authors: Chowdhry S, Nazmy MH, Meakin PJ, Dinkova-Kostova AT, Walsh SV, Tsujita T, Dillon JF, Ashford ML, Hayes JD Tags: Free Radic Biol Med Source Type: journals

Dietary nitrate reduces maximal oxygen consumption while maintaining work performance at maximal exercise.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusion: A moderate dietary dose of nitrate significantly reduces VO(2)max during maximal exercise with a large active muscle mass. This reduction occurred with a trend towards increased time to exhaustion implying that two separate mechanisms are involved; one that reduces VO(2)max and another that improves the energetic function of the working muscles. PMID: 19913611 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - November 11, 2009 Category: Biology Authors: Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B Tags: Free Radic Biol Med Source Type: journals

Ferroportin1 but not hephaestin contributes to iron accumulation in a cell model of Parkinson's disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Iron induced oxidative stress was thought to play a crucial role in the pathogenesis of Parkinson's disease (PD). Based on our previously in vivo experiments that iron transporters ferroportin1 (FP1) and hephaestin (HP) down-regulations might account for the nigral iron accumulation in 6-hydroxydopamine (6-OHDA) lesioned animal models, in the present study we investigated whether FP1 and HP were involved in cellular iron accumulation and the underlying mechanisms in a cell model of PD. The findings showed that 6-OHDA induced FP1 and HP down-regulation, followed by decreased iron efflux and iron accumulation in primary ...
Source: Free Radical Biology and Medicine - November 10, 2009 Category: Biology Authors: Song N, Wang J, Jiang H, Xie J Tags: Free Radic Biol Med Source Type: journals

Reactions of Nitrite in Erythrocyte Suspensions Measured by Membrane Inlet Mass Spectrometry.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The reactions of nitrite with deoxygenated human erythrocytes were examined using membrane inlet mass spectrometry to detect the accumulation of NO in extracellular solution. In this method an inlet utilizing a silicon rubber membrane is submerged in cell suspensions and allows NO to pass from extracellular solution into the mass spectrometer. This provides a direct, continuous, and quantitative determination of nitric oxide concentrations over long periods without the necessity of purging the suspension with inert gas. We have not observed accumulation of NO when compared with controls on a physiologically relevant ti...
Source: Free Radical Biology and Medicine - November 10, 2009 Category: Biology Authors: Mikulski R, Tu C, Swenson ER, Silverman DN Tags: Free Radic Biol Med Source Type: journals

Benzene and dopamine catechol quinones could initiate cancer or neurogenic disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Catechol quinones of estrogens react with DNA by 1,4-Michael addition to form depurinating N3Ade and N7Gua adducts. Loss of these adducts from DNA creates apurinic sites that can generate mutations leading to cancer initiation. We compared reaction of the catechol quinones of the leukemogenic benzene (CAT-Q) and N-acetyldopamine (NADA-Q) with dG or DNA. NADA was used to prevent intramolecular cyclization of dopamine quinone. Reaction of CAT-Q or NADA-Q with dG at pH 4 afforded CAT-4-N7dG or NADA-6-N7dG, which lost deoxyribose with a half-life of 3 h to form CAT-4-N7Gua or 4 h to form NADA-6-N7Gua. When CAT-Q or NADA-Q ...
Source: Free Radical Biology and Medicine - November 9, 2009 Category: Biology Authors: Zahid M, Saeed M, Rogan EG, Cavalieri EL Tags: Free Radic Biol Med Source Type: journals

Nitration of the Mitochondrial Complex I Subunit NDUFB8 Elicits RIP1 and 3-Mediated Necrosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Nitric oxide and other reactive nitrogen species target multiple sites in the mitochondria to impact cellular bioenergetics and survival. Kinetic imaging studies revealed that NO from either activated macrophages or donor compounds rapidly diffuses to the mitochondria, causing a dose dependent progressive increase in NO-dependent DAF fluorescence that corresponded to mitochondrial membrane potential loss, and initiated alterations in cellular bioenergetics that ultimately led to necrotic cell death. Cellular dysfunction is mediated by an elevated 3-nitrotyrosine signature of the mitochondrial complex I subunit NDUFB8, ...
Source: Free Radical Biology and Medicine - November 5, 2009 Category: Biology Authors: Davis CW, Hawkins BJ, Ramasamy S, Irrinki KM, Cameron BA, Islam K, Daswani VP, Doonan PJ, Manevich Y, Madesh M Tags: Free Radic Biol Med Source Type: journals

Variation in gene expression profiles of human monocytic U937 cells exposed to various fluxes of nitric oxide.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We examined early and late alterations in gene expression patterns and phosphorylation levels of key regulators of selected signaling pathways in U937 cells exposed to different (.)NO fluxes. cDNA microarray analysis and real-time quantitative PCR identified NO-sensitive 45 genes (>/=2-fold change) among which KLF2, KLF6, TSC22D3, DDIT4, MKP-5 (up-regulated), KIF23, histone H4, ARL6IP2, CLNS1A, SLC7A6, CDKN3, SRP19, BCL11A (down-regulated) have not been reported before. For two selected genes, KLF2 and DDIT4, the sensitivity to (.)NO was also proved at the protein level. Among the examined genes, only KLF2 had a higher ...
Source: Free Radical Biology and Medicine - November 2, 2009 Category: Biology Authors: Turpaev K, Glatigny A, Bignon J, Delacroix H, Drapier JC Tags: Free Radic Biol Med Source Type: journals

Induction of COX-2/PGE(2)/IL-6 is crucial for cigarette smoke extract-induced airway inflammation: Role of TLR4-dependent NADPH oxidase activation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Exposure to cigarette smoke extract (CSE) leads to airway and lung inflammation through oxidant-antioxidant imbalance. Cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)) have been demonstrated to play critical roles in respiratory inflammation. Here, we show that COX-2/PGE(2)/IL-6 induction is dependent on Toll-like receptor 4 (TLR4)/NADPH oxidase signaling in human tracheal smooth muscle cells (HTSMCs). CSE induced COX-2 expression in vitro in HTSMCs and in vivo in the airways of mice. CSE also directly caused an increase in TLR4. Moreover, CSE-regulated COX-2, PGE(2), and IL-6 generation were inhibited by pretr...
Source: Free Radical Biology and Medicine - November 2, 2009 Category: Biology Authors: Lin CC, Lee IT, Yang YL, Lee CW, Kou YR, Yang CM Tags: Free Radic Biol Med Source Type: journals

Dps proteins prevent Fenton mediated oxidative damage by trapping hydroxyl radicals within the protein shell.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Dps proteins (DNA binding proteins from starved cells) belong to a widespread bacterial family expressed under nutritional and oxidative stress conditions. In particular, Dps proteins protect DNA against Fenton mediated oxidative stress as they catalyze iron oxidation by hydrogen peroxide at highly conserved ferroxidase centers and thus reduce significantly hydroxyl radicals production. The present work investigates the possible generation of intraprotein radicals during the ferroxidation reaction by Escherichia coli and Listeria innocua Dps, two representative members of the family. Stopped flow analyses show that the...
Source: Free Radical Biology and Medicine - November 2, 2009 Category: Biology Authors: Bellapadrona G, Ardini M, Ceci P, Stefanini S, Chiancone E Tags: Free Radic Biol Med Source Type: journals

Increased levels of cell-free hemoglobin, oxidation markers, and the antioxidative heme scavenger alpha(1)-microglobulin in preeclampsia.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Preeclampsia is a major cause of morbidity and mortality during pregnancy. To date, the pathogenesis of the disease is not fully understood. Recent studies show that preeclampsia is associated with overexpression of hemoglobin genes alpha2 and gamma and accumulation of the protein in the vascular lumen of the placenta. Hypothesizing that cell-free hemoglobin leaks from the placenta into the maternal circulation and contributes to the endothelial damage and symptoms by inducing oxidative stress, we analysed fetal and adult hemoglobin (HbF, HbA), haptoglobin, oxidation markers and the heme scavenger and antioxidant alpha...
Source: Free Radical Biology and Medicine - October 29, 2009 Category: Biology Authors: Olsson MG, Centlow M, Rutardóttir S, Stenfors I, Larsson J, Hosseini-Maaf B, Olsson ML, Hansson SR, Akerström B Tags: Free Radic Biol Med Source Type: journals

Improvement of the sensitivity of EPR spin trapping in biological systems by cyclodextrins: A model study with thylakoids and photosystem II particles.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Electron paramagnetic resonance (EPR) spin trapping spectroscopy is an important method used in free radical research, however, its application in biological systems is hindered by EPR silencing of spin adducts. Previous studies in superoxide-generating chemical systems have shown that spin adducts can be partially stabilized by cyclodextrins. In this work, for the first time, this proposed protective effect of cyclodextrins is investigated in a real biological sample - in isolated thylakoid membranes and photosystem II (PSII) particles with EMPO as a spin trap. It has been shown that i) randomly methylated-beta-cyclod...
Source: Free Radical Biology and Medicine - October 29, 2009 Category: Biology Authors: Snyrychová I Tags: Free Radic Biol Med Source Type: journals

A key role for mitochondria in endothelial signaling by plasma cysteine/cystine redox potential.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The redox potential (E(h)) of the plasma cysteine/cystine (Cys/CySS) couple (E(h)CySS) is oxidized in association with risk factors for cardiovascular disease (CVD), including age, smoking, type II diabetes, obesity, and alcohol abuse. Previous in vitro findings support a cause-effect relationship of extracellular E(h)CySS in cell signaling pathways associated with CVD, including those controlling monocyte adhesion to endothelial cells. In the present study, we provide evidence that mitochondria are a major source of reactive oxygen species (ROS) in the signaling response to a more oxidized extracellular E(h)CySS. This...
Source: Free Radical Biology and Medicine - October 29, 2009 Category: Biology Authors: Go YM, Park H, Koval M, Orr M, Reed M, Liang Y, Smith D, Pohl J, Jones DP Tags: Free Radic Biol Med Source Type: journals

A Novel Role for Cytochrome c: Efficient Catalysis of S-Nitrosothiol Formation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
While S-nitrosothiols are regarded as important elements of many NO-dependent signal transduction pathways, the physiological mechanism of their formation remains elusive. Here, we demonstrate a novel mechanism by which cytochrome c may represent an efficient catalyst of S-nitrosation in vivo. In this mechanism, initial binding of GSH to ferric cytochrome c is followed by reaction of NO with this complex, yielding ferrous cytochrome c and GSNO. We show that when submitochondrial particles or cell lysates are exposed to NO in the presence of cytochrome c, there is a robust formation of protein S-nitrosothiols. In the ca...
Source: Free Radical Biology and Medicine - October 28, 2009 Category: Biology Authors: Basu S, Keszler A, Azarova NA, Nwanze N, Perlegas A, Shiva S, Broniowska KA, Hogg N, Kim-Shapiro DB Tags: Free Radic Biol Med Source Type: journals

Ethanol withdrawal increases glutathione adducts of 4-hydroxy-2-hexenal but not 4-hydroxyl-2-nonenal in the rat cerebral cortex.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study rats received an ethanol containing diet for six weeks followed by withdrawal ranging between 0 to 7 days. GSHHE content was elevated (>350%) in the cerebral cortex following two days of withdrawal with no change in GSHNE. The levels of GSHHE were significantly greater (2 to 20-fold) than GSHNE in multiple brain regions. Experiments demonstrated that intoxication and withdrawal did not alter the enzymatic rate of formation of GSHHE or GSHNE, but the rate of formation of GSHHE was higher (~50%) than that of GSHNE. These results indicate that selective oxidative damage to n-3 PUFA occurs in the cerebral cort...
Source: Free Radical Biology and Medicine - October 27, 2009 Category: Biology Authors: Long EK, Rosenberger TA, Picklo MJ Tags: Free Radic Biol Med Source Type: journals

A role for Bach1 and HO-2 in suppression of basal and UVA-induced HO-1 expression in human keratinocytes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Ultraviolet A (UVA) radiation is an oxidizing agent that strongly induces the heme oxygenase 1 (HO1) gene and expression of the protein in cultured human skin fibroblasts but weakly induces it in skin keratinocytes. Lower basal levels of HO-1 and much higher basal levels of HO-2 protein are observed in keratinocytes compared with fibroblasts. Using both over-expression and knock-down approaches, we demonstrate that HO-2 modulates basal and UVA-induced HO-1 protein levels while HO-1 levels do not affect HO-2 levels in skin fibroblasts and keratinocytes. Silencing of Bach1 strongly increases HO-1 levels in HaCaT transfor...
Source: Free Radical Biology and Medicine - October 26, 2009 Category: Biology Authors: Li Zhong J, Raval C, Edwards GP, Tyrrell RM Tags: Free Radic Biol Med Source Type: journals

Increased thrombin-induced polymerization of fibrinogen associated with high protein carbonyl levels in plasma from patients post myocardial infarction.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we have examined representative plasma samples from this group of patients. We show that carbonyls are formed preferentially on fibrinogen and that there is a strong correlation between fibrinogen and total plasma protein carbonyls. Functional properties of fibrinogen isolated from post myocardial plasmas were investigated by measuring thrombin-catalysed polymerization. Fibrinogen from plasma with upper quartile protein carbonyls (mean 0.16 nmol/mg protein) polymerized ~1.4 times more rapidly and gave 1.4 fold higher maximum turbidity (12 per group, p<0.001) than fibrinogen from lower quartile carbonyl pl...
Source: Free Radical Biology and Medicine - October 23, 2009 Category: Biology Authors: Paton LN, Mocatta TJ, Richards AM, Winterbourn CC Tags: Free Radic Biol Med Source Type: journals

Activation of vascular Endothelial Nitric Oxide Synthase and Heme Oxygenase-1 Expression by electrophilic nitro-fatty acids.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Reactive oxygen species mediate a decrease in nitric oxide (NO) bioavailability and endothelial dysfunction, with secondary oxidized and nitrated byproducts of these reactions contributing to the pathogenesis of numerous vascular diseases. While oxidized lipids and lipoproteins exacerbate inflammatory reactions in the vasculature, in stark contrast the nitration of polyunsaturated fatty acids and complex lipids yield electrophilic products that exhibit pluripotent anti-inflammatory signaling capabilities acting via both cGMP-dependent and -independent mechanisms. Herein we report that nitro-oleic acid (OA-NO(2)) treatm...
Source: Free Radical Biology and Medicine - October 23, 2009 Category: Biology Authors: Khoo NK, Rudolph V, Cole MP, Golin-Bisello F, Schopfer FJ, Woodcock SR, Batthyany C, Freeman BA Tags: Free Radic Biol Med Source Type: journals

Oxidants Induce Alternative Splicing of alpha-Synuclein: Implications for Parkinson's Disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
alpha-Synuclein (alpha-syn) is a presynaptic protein that is widely implicated in the pathophysiology of Parkinson's disease (PD). Emerging evidence indicates a strong correlation between alpha-syn aggregation and proteasomal dysfunction as one of the major pathways responsible for destruction of the dopamine neurons. Using Parkinsonism mimetics (MPP(+), rotenone) and related oxidants, we have identified an oxidant-induced alternative splicing of alpha-syn mRNA, generating a shorter isoform of alpha-syn with deleted exon-5 (112-syn). This spliced isoform has an altered localization and profoundly inhibits proteasomal f...
Source: Free Radical Biology and Medicine - October 23, 2009 Category: Biology Authors: Kalivendi SV, Yedlapudi D, Hillard CJ, Kalyanaraman B Tags: Free Radic Biol Med Source Type: journals

PKC-delta controls the fMLF-induced overproduction of superoxide by neutrophils.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Anti-microbial defense by neutrophils implicates the production of reactive oxygen species. Neutrophil responses can be modulated by agonists like bacterial peptides and pro-inflammatory factors that modulate neutrophil activity and survival. We evaluated the production of superoxide anions (O(2)(-)) in response to fMLF by normal human neutrophils after 3 days of preincubation with GM-CSF+IL-4+TNF-alpha (survival medium). After 3 days of incubation with survival medium, long-lived neutrophils produced up to 6 times more O(2)(-) relative to control neutrophils in response to fMLF and WKYMVM. This augmented response to f...
Source: Free Radical Biology and Medicine - October 22, 2009 Category: Biology Authors: Matron C, Chakravarti A, Allaeys I, Poubelle PE Tags: Free Radic Biol Med Source Type: journals

Antioxidants Rescue Photoreceptors in Rd1 Mice: Relationship with Thiol Metabolism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We have previously shown that the use of a combination of antioxidants delayed the degeneration process in rd1mouse retina. In an effort to understand the mechanism of action of these substances (zeaxanthin, lutein, alpha lipoic acid, glutathione and Lycium barbarum extract) the changes in the levels of several proteins and oxidative stress markers in the rd1 retina have been studied. The treatment increased glutathione peroxidase activity and glutathione levels, and decreased cystine concentrations in rd1 retinas. Considering all the results obtained from treated and untreated animals, a high correlation was present b...
Source: Free Radical Biology and Medicine - October 22, 2009 Category: Biology Authors: Miranda M, Arnal E, Ahuja S, Ekström P, Bosch-Morell F, van Veen T, Romero FJ Tags: Free Radic Biol Med Source Type: journals

Puerarin Attenuates High Glucose and Diabetes-induced Vascular Smooth Muscle Cell Proliferation Via Blocking PKC-beta2/Rac-1-Dependent Signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Oxidative stress has been implicated in several steps leading to the development of diabetic vascular complications. The purpose of current study was to determine the efficacy and the possible mechanism of puerarin on high glucose (25 mM, HG)-induced proliferation of cultured rat vascular smooth muscle cells (VSMCs) and neointimal formation in a carotid arterial balloon injury model of obese Zucker rats. Our data demonstrated that puerarin significantly inhibited rat VSMCs proliferation as well as reactive oxygen species (ROS) generation and NAPDH oxidase activity induced by HG treatment. Further studies revealed that ...
Source: Free Radical Biology and Medicine - October 22, 2009 Category: Biology Authors: Zhu LH, Wang L, Wang D, Jiang H, Tang QZ, Yan L, Bian ZY, Wang XA, Li H Tags: Free Radic Biol Med Source Type: journals

Consequences of long-term oral administration of the mitochondria-targeted antioxidant MitoQ to wild-type mice.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The mitochondria-targeted quinone MitoQ protects mitochondria in animal studies of pathologies in vivo, and is being developed as a human therapy. However, it is unclear if the protective action of MitoQ is entirely due to its antioxidant properties, since long-term MitoQ administration may alter whole body metabolism and gene expression. To address this point, we administered high levels of MitoQ orally to wild-type C57BL/6 mice for up to 28 weeks, and investigated the effects on whole body physiology, metabolism, and gene expression, finding no measurable deleterious effects. In addition, because antioxidants can act...
Source: Free Radical Biology and Medicine - October 22, 2009 Category: Biology Authors: Rodriguez-Cuenca S, Cochemé HM, Logan A, Abakumova I, Prime TA, Rose C, Vidal-Puig A, Smith AC, Rubinsztein DC, Fearnley IM, Jones BA, Pope S, Heales SJ, Lam BY, Neogi SG, McFarlane I, James AM, Smith RA, Murphy MP Tags: Free Radic Biol Med Source Type: journals

In Vivo Oxidative Stress in Brain of Alzheimer Disease Transgenic Mice: Requirement for Methionine 35 in Amyloid Beta-Peptide Of APP.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Numerous studies have demonstrated oxidative damage in the central nervous system in subjects with Alzheimer disease and in animal models of this dementing disorder. In the current study, we show that transgenic mice modeling Alzheimer disease-PDAPP mice with Swedish and Indiana mutations in human amyloid precursor protein (APP)-develop oxidative damage in brain, including elevated levels of protein oxidation (indexed by protein carbonyls and 3-nitrotyrosine) and lipid peroxidation (indexed by protein-bound 4-hydroxy-2-nonenal). This oxidative damage requires the presence of a single methionine residue at position 35 o...
Source: Free Radical Biology and Medicine - October 22, 2009 Category: Biology Authors: Butterfield DA, Galvan V, Lange MB, Tang H, Sowell RA, Spilman P, Fombonne J, Gorostiza O, Zhang J, Sultana R, Bredesen DE Tags: Free Radic Biol Med Source Type: journals

Isoprostanes in Fetal and Neonatal Health and Disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Isoprostanes are prostaglandin-like bioactive molecules generated via nonenzymatic peroxidation of lipid membrane-derived arachidonic acid by free radicals and reactive oxygen species. Their cognate receptors, biological actions, and signaling pathways are poorly understood. Aside from being sensitive and specific biomarkers of oxidative stress, E- and F-ring isoprostanes have important biological functions and likely mediate many of the disease-related pathological changes for which they are used as indicators. The biochemical pathways involved in isoprostane formation, their pathogenetic relevance to adult disease st...
Source: Free Radical Biology and Medicine - October 22, 2009 Category: Biology Authors: Belik J, Luis GE, Vizcaino FP, Villamor E Tags: Free Radic Biol Med Source Type: journals

Effects of water-filtered infrared-A (wIRA) irradiation on human fibroblasts.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Infrared is a substantial part of the solar energy output reaching the earth surface. Therefore, exposure of humans to infrared is common. However, whether and how infrared or infrared A is acting on human skin cells is still under debate. Recently the generation of reactive oxygen species by water-filtered-infrared-A (wIRA)-irradiation was postulated. wIRA shows a similar spectral distribution as solar irradiation at earth's surface. Thus, the need of protection of human skin from both solar and artificially generated infrared A radiation was concluded. Here we demonstrate that in human dermal fibroblasts this reactiv...
Source: Free Radical Biology and Medicine - October 21, 2009 Category: Biology Authors: Jung T, Höhn A, Piazena H, Grune T Tags: Free Radic Biol Med Source Type: journals

Evidence against tetrahydrobiopterin depletion of vascular tissue exposed to nitric oxide/superoxide or nitroglycerin.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Several cardiovascular disorders, including atherosclerosis and tolerance to the antianginal drug nitroglycerin (GTN) may be associated with generation of superoxide anions which react with nitric oxide (NO) to yield peroxynitrite. According to a widely held view, oxidation of tetrahydrobiopterin (BH(4)) by peroxynitrite causes uncoupling of endothelial NO synthase (eNOS), resulting in reduced NO bioavailability and endothelial dysfunction in conditions of oxidative stress. In the present study we determined the levels of reduced biopterins and endothelial function in cultured cells exposed to peroxynitrite and GTN as ...
Source: Free Radical Biology and Medicine - October 21, 2009 Category: Biology Authors: Schmidt K, Rehn M, Stessel H, Wölkart G, Mayer B Tags: Free Radic Biol Med Source Type: journals

Ascorbate protects endothelial barrier function during septic insult: Role of protein phosphatase type 2A.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, ascorbate acts within microvascular endothelial cells to inhibit septic stimulation of oxidant production by NADPH oxidase and thereby prevents PP2A activation, PP2A-dependent dephosphorylation and redistribution of occludin, and disruption of the endothelial barrier. PMID: 19840845 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - October 15, 2009 Category: Biology Authors: Han M, Pendem S, Teh SL, Sukumaran DK, Wu F, Wilson JX Tags: Free Radic Biol Med Source Type: journals

Stimulation of mitochondrial reactive oxygen species production by unesterified, unsaturated fatty acids in defective human spermatozoa.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study we demonstrate that defective human sperm populations are characterized by high cellular contents of both esterified and unesterified fatty acids and a decrease in the proportion of the total fatty acid pool made up by docosahexaenoic acid. The free unsaturated fatty acid content of these cells was positively correlated with the induction of mitochondrial superoxide generation (P < 0.001). This relationship was causal and mediated by the range of unesterified, unsaturated fatty acids that are present in human spermatozoa. Thus direct exposure of these cells to free unsaturated fatty acids stimulated mitoch...
Source: Free Radical Biology and Medicine - October 14, 2009 Category: Biology Authors: Koppers AJ, Garg ML, Aitken RJ Tags: Free Radic Biol Med Source Type: journals

Role of oxidative stress in vinorelbine-induced vascular endothelial cell injury.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Vinorelbine (VNR), a vinca alkaloid anticancer drug, often causes vascular injury such as venous irritation, vascular pain, phlebitis and necrotizing vasculitis. The purpose of this study was to identify mechanisms that mediate the cell injury induced by VNR in porcine aorta endothelial cells (PAECs). PAECs were exposed to VNR for 10 min followed by further incubation in serum-free medium without VNR. The exposure to VNR (0.3-30 muM) decreased the cell viability concentration- and time-dependently. The incidence of apoptotic cells significantly increased at 12 h after transient exposure to VNR. VNR also increased the a...
Source: Free Radical Biology and Medicine - October 14, 2009 Category: Biology Authors: Yamada T, Egashira N, Imuta M, Yano T, Yamauchi Y, Watanabe H, Oishi R Tags: Free Radic Biol Med Source Type: journals

Cinnamaldehydes inhibit thioredoxin reductase and induce Nrf2: potential candidates for cancer therapy and chemoprevention.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, a series of ortho-substituted cinnamaldehyde analogs was synthesized and screened for antiproliferative and thioredoxin reductase (TrxR) inhibitory activities. While CA was weakly cytotoxic and TrxR-inhibiting, hydroxy and benzoyloxy substitutions resulted in analogs with enhanced antiproliferative activity paralleling increased potencies in TrxR inactivation. A novel analog 5-fluoro-2-hydroxycinnamaldehyde (FHCA) was identified to exhibit strongest antitumor effect (GI(50) 1.6 muM in HCT 116 cells) and TrxR inhibition (IC(50) 7 muM, 1 h incubation with recombinant TrxR). CA and its 2-hydroxy and 2-benzoylox...
Source: Free Radical Biology and Medicine - October 14, 2009 Category: Biology Authors: Chew EH, Nagle AA, Zhang Y, Scarmagnani S, Palaniappan P, Bradshaw TD, Holmgren A, Westwell AD Tags: Free Radic Biol Med Source Type: journals

Urinary analysis of 8-oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine by isotope-dilution LC-MS/MS with automated solid-phase extraction: study of 8-oxo-7,8-dihydroguanine stability.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A highly sensitive quantitative method based on LC-MS/MS was developed to simultaneously and directly measure 8-oxo-7,8-dihydroguanine (8-oxoGua) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) in urine. It was found that 8-oxoGua could be artifactually generated from 8-oxodGuo during ionization process due to both in-source thermolysis and collisionally induced dissociation. Our method applied a two-stage wash procedure in the on-line solid-phase extraction (SPE) system not only eliminated ion suppression but also prevented artifactual interference of 8-oxoGua from 8-oxodGuo by eluting the analytes individually. W...
Source: Free Radical Biology and Medicine - October 13, 2009 Category: Biology Authors: Hu CW, Chao MR, Sie CH Tags: Free Radic Biol Med Source Type: journals

Marginal zinc deficiency increases oxidative DNA damage in the prostate following chronic exercise.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Approximately 12% of Americans do not consume recommended level for zinc and could be at risk for marginal zinc deficiency. Zinc functions in antioxidant defense and DNA repair, and could be important for prostate health. We hypothesized that marginal zinc deficiency sensitizes the prostate to oxidative stress and DNA damage. Rats were fed a zinc-adequate (ZA, 30mg Zn/kg) or marginally zinc-deficient (MZD, 5-6mg Zn/kg) diet for 6wk. MZD increased p53 and PARP expressions but no change in 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were detected. To examine the susceptibility to exogenous oxidative stress, rats fed a ZA...
Source: Free Radical Biology and Medicine - October 13, 2009 Category: Biology Authors: Song Y, Elias V, Loban A, Scrimgeour AG, Ho E Tags: Free Radic Biol Med Source Type: journals

pO(2) Dependent NO Production Determines OPPC Activity in Macrophages.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Stimulated macrophages produce nitric oxide (NO) via inducible nitric oxide synthase (iNOS) using molecular O(2), L-arginine, and NADPH. Exposure of macrophages to hypoxia decreases NO production within seconds suggesting substrate limitation as the mechanism. Conflicting data exist regarding the effect of pO(2) on NADPH production via the oxidative pentose phosphate cycle (OPPC). Therefore, the present studies were developed to determine whether NADPH could be limiting for NO production under hypoxia. Production of NO metabolites (NOx) and OPPC activity by RAW 264.7 cells was significantly increased by stimulation wit...
Source: Free Radical Biology and Medicine - October 8, 2009 Category: Biology Authors: Robinson MA, Tuttle SW, Otto CM, Koch CJ Tags: Free Radic Biol Med Source Type: journals

alpha-tocopherol beta-Oxidation Localized to Rat Liver Mitochondria.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Approximately 40% of Americans take dietary supplements, including vitamin E (alpha-tocopherol). Unlike other fat-soluble vitamins, alpha-tocopherol is not accumulated to toxic levels. Rather tissue levels are tightly regulated, in part via increased hepatic metabolism and excretion that could, theoretically, alter metabolism of drugs, environmental toxins and other nutrients. To date, in vivo subcellular location(s) of alpha-tocopherol metabolism have not been identified. The proposed pathway of alpha-tocopherol metabolism proceeds via omega-hydroxylation to 13'-OH-alpha-tocopherol, followed by successive rounds of be...
Source: Free Radical Biology and Medicine - October 7, 2009 Category: Biology Authors: Mustacich DJ, Leonard SW, Patel NK, Traber MG Tags: Free Radic Biol Med Source Type: journals

Quantitation of Mercapturic Acid Conjugates of 4-Hydroxy-2-Nonenal and 4-Oxo-2-Nonenal Metabolites in a Smoking Cessation Study.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The breakdown of polyunsaturated fatty acids (PUFAs) under conditions of oxidative stress results in the formation of lipid peroxidation (LPO) products. These LPO products such as 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE) can contribute to the development of cardiovascular and neurodegenerative diseases and cancer. Conjugation with glutathione, followed by further metabolism to mercapturic acid (MA) conjugates, can mitigate the effects of these LPO products in disease development by facilitating their excretion from the body. We have developed a quantitative method to simultaneously assess levels of 4-oxo-2-n...
Source: Free Radical Biology and Medicine - October 7, 2009 Category: Biology Authors: Kuiper HC, Langsdorf BL, Miranda CL, Joss J, Jubert C, Mata JE, Stevens JF Tags: Free Radic Biol Med Source Type: journals

The Reaction between Nitric Oxide, Glutathione and Oxygen in the Presence and Absence of Protein: How are S-Nitrosothiols Formed?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study we have re-investigated this reaction using both experiment and simulation and conclude that: (i) S-Nitrosation through radical and non-radical pathways is occurring simultaneously (ii) S-Nitrosation through direct addition of NO to thiol does not occur to any meaningful extent and (iii) protein hydrophobic environments do not catalyze or enhance S-nitrosation of either themselves or of glutathione. We conclude that S-nitrosation and disulfide formation in this system occur only after the initial reaction between NO and oxygen to form nitrogen dioxide, and that hydrophobic protein environments are unlikely to...
Source: Free Radical Biology and Medicine - October 7, 2009 Category: Biology Authors: Keszler A, Zhang Y, Hogg N Tags: Free Radic Biol Med Source Type: journals

Alternate-day fasting protects the rat heart against the age-induced inflammation and fibrosis by inhibiting oxidative damage and NF-kB activation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The free radical theory of aging is currently one of the most popular. In parallel, many studies have demonstrated the association of fibrosis and increased oxidative stress in the pathogenesis of some chronic human diseases, and fibrosis is often characteristic of aging tissues. One of the few interventions that effectively slows aging is calorie restriction and the protection against the age-associated increase of oxidative stress remains one of the foremost hypotheses to explain this action. As an alternative to traditional calorie restriction, another dietary regimen, termed alternate-day fasting, has also been tes...
Source: Free Radical Biology and Medicine - October 6, 2009 Category: Biology Authors: Castello L, Froio T, Maina M, Cavallini G, Biasi F, Leonarduzzi G, Donati A, Bergamini E, Poli G, Chiarpotto E Tags: Free Radic Biol Med Source Type: journals

Control of hypoxia-induced tumor cell adhesion by cytophilic human catalase.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hypoxia-induced reactive oxygen species (ROS)-mediated expression of a variety of genes in endothelial cells has been suggested to be involved in abnormal cell adhesion. To prevent this by accelerated binding of catalase to endothelial cells, human catalase (hCAT), an enzyme catalyzing the decomposition of hydrogen peroxide, was fused with three repeats of arginine-glycine-aspartic acid peptide or nona arginine peptide at the C-terminal to obtain hCAT-(RGD)3 and hCAT-R9, respectively. Human CAT and its derivatives were expressed in yeast Pichia pastoris and purified. The specific activity and secondary structure of hCA...
Source: Free Radical Biology and Medicine - October 1, 2009 Category: Biology Authors: Yata T, Nishikawa M, Nishizaki C, Oku M, Yurimoto H, Sakai Y, Takakura Y Tags: Free Radic Biol Med Source Type: journals

Oxidative stress and glutathione in TGF-beta-mediated fibrogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Transforming growth factor beta (TGF-beta) is the most potent and ubiquitous profibrogenic cytokine and its expression is increased in almost all the fibrotic diseases and in experimental fibrosis models. TGF-beta increases ROS production and decreases the concentration of glutathione (GSH), the most abundant intracellular free thiol and an important antioxidant, in various types of cells, which mediates many of TGF-beta's fibrogenic effects. A decreased GSH concentration is also observed in human fibrotic diseases and in experimental fibrosis models. Although the biological significance of GSH depletion in the develop...
Source: Free Radical Biology and Medicine - September 30, 2009 Category: Biology Authors: Liu RM, Pravia KA Tags: Free Radic Biol Med Source Type: journals

Site-specific hypochlorous acid-induced oxidation of recombinant human myoglobin affects specific amino acid residues and the rate of cytochrome b(5)-mediated heme reduction.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study has (i) compared wild type and a Cys110Ala variant of HMb to assess the influence of Cys110 on HOCl-induced amino acid modification, and (ii) determined whether HOCl-oxidation of HMb affects the rate of ferric heme reduction by cytochrome b(5). For wild type HMb (HOCl:Mb ratio of 5:1 mol/mol), Cys110 was preferentially oxidized to a homodimeric or cysteic acid product-sulfenic/sulfinic acids were not detected. At a HOCl:Mb ratio 10:1 mol/mol, methionine (Met) oxidation was detected, and this was enhanced in the Cys110Ala variant. Tryptophan (Trp) oxidation was detected only in the Cys110Ala variant at the highes...
Source: Free Radical Biology and Medicine - September 30, 2009 Category: Biology Authors: Szuchman-Sapir AJ, Pattison DI, Davies MJ, Witting PK Tags: Free Radic Biol Med Source Type: journals

Reduced oxygen tension results in reduced human T cell proliferation and increased intracellular oxidative damage and susceptibility to apoptosis upon activation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we report a reduced proliferative response and increased apoptosis susceptibility following T cell activation at 2% oxygen compared to in air. To explain this observation, we tested the hypothesis of an impaired efficacy of intracellular protective mechanisms including antioxidant levels, oxidized protein repair (methionine sulfoxide reductases) and degradation (proteasome) activities. Indeed, following activation, there was a significant accumulation of intracellular oxidized proteins at more physiological oxygen levels concomitant with a reduced GSH:GSSG ratio. Proteasome and methionine sulfoxide reductase...
Source: Free Radical Biology and Medicine - September 27, 2009 Category: Biology Authors: Larbi A, Cabreiro F, Zelba H, Marthandan S, Combet E, Friguet B, Petropoulos I, Barnett Y, Pawelec G Tags: Free Radic Biol Med Source Type: journals

Polychlorinated biphenyl (PCB)-induced oxidative stress and cytotoxicity can be mitigated by antioxidants following exposure.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PCBs and PCB metabolites have been suggested to cause cytotoxicity by inducing oxidative stress but the effectiveness of antioxidant intervention following exposure is not established. Exponentially growing MCF-10A human breast and RWPE-1 human prostate epithelial cells continuously exposed for 5 days to 3 microM PCBs [Aroclor 1254, PCB153, and the 2-(4-chlorophenyl)-1,4-benzoquinone metabolite of PCB3 (4ClBQ)] were found to exhibit growth inhibition and clonogenic cell killing, with 4ClBQ having the most pronounced effects. These PCBs were also found to increase steady-state levels intracellular O(2)(-) and H(2)O(2) (...
Source: Free Radical Biology and Medicine - September 27, 2009 Category: Biology Authors: Zhu Y, Kalen AL, Li L, Lehmler HJ, Robertson LW, Goswami PC, Spitz DR, Aykin-Burns N Tags: Free Radic Biol Med Source Type: journals

Hyperoxia augments ER stress induced cell death independent of BiP loss.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cytotoxic reactive oxygen species are constantly formed as a byproduct of aerobic respiration, and are thought to contribute to aging and disease. Cells respond to oxidative stress by activating various pathways, whose balance is important for adaptation, or induction of cell death. Our lab recently reported that BiP (GRP78), a proposed negative regulator of the unfolded protein response (UPR), declines during hyperoxia, a model of chronic oxidative stress. Here, we investigate whether exposure to hyperoxia, and consequently loss of BiP, activates the UPR or sensitizes cells to ER stress. Evidence is provided that hype...
Source: Free Radical Biology and Medicine - September 24, 2009 Category: Biology Authors: Gewandter JS, Staversky RJ, O'Reilly MA Tags: Free Radic Biol Med Source Type: journals

Fibroblasts from Long-Lived Mutant Mice Show Diminished ERK1/2 Phosphorylation But Exaggerated Induction of Immediate Early Genes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Skin-derived fibroblasts from long-lived mutant mice, including the Snell dwarf mice and mice defective in growth hormone receptor ("GHRKO"), are resistant to death induced by oxidative stresses or by UV light, but the molecular mechanism for their stress resistance is unknown. The present study showed that phosphorylation of the stress-activated protein kinases ERK1/2 induced by peroxide, cadmium, or paraquat was attenuated in cells from these mice. Induction of ERK phosphorylation by UV light was not altered in the Snell dwarf cells, and neither JNK nor p38 kinases showed increased phosphorylation in response to any ...
Source: Free Radical Biology and Medicine - September 24, 2009 Category: Biology Authors: Sun LY, Steinbaugh MJ, Masternak MM, Bartke A, Miller RA Tags: Free Radic Biol Med Source Type: journals

A Critical Evaluation of cpYFP as a Probe for Superoxide.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19778603 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - September 20, 2009 Category: Biology Authors: Muller FL Tags: Free Radic Biol Med Source Type: journals

Pro-oxidant and pro-apoptotic effects of cholesterol oxidation products on human colonic epithelial cells: a potential mechanism of inflammatory bowel disease progression.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
With the aim to investigate if cholesterol oxidation products could contribute to the pathogenesis of the intestinal epithelial barrier dysfunction occurring in human inflammatory bowel disease (IBD), differentiated versus undifferentiated CaCo-2 cells, an accepted model for human intestinal epithelial cells, were challenged with a dietary representative mixture of oxysterols. Only differentiated colonic cells resulted to be susceptible to the pro-apoptotic action of the oxysterol mixture, checked both by enzymatic and morphological methods, mainly because of a very low AKT phosphorylation pathway as to the undifferent...
Source: Free Radical Biology and Medicine - September 20, 2009 Category: Biology Authors: Biasi F, Mascia C, Astegiano M, Chiarpotto E, Nano M, Vizio B, Leonarduzzi G, Poli G Tags: Free Radic Biol Med Source Type: journals

Making and Working with Hydrogen Sulfide The chemistry and generation of hydrogen sulfide in vitro and its measurement in vivo: A review.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hydrogen sulfide is rapidly emerging as an important vasoactive mediator formed in health and disease. Its biological action is centered on its reactivity with heme-proteins and its ability to activate K(ATP) channels. Hydrogen sulfide is a signalling molecule of the inflammatory and nervous systems, and in particular the cardiovascular system where it regulates vascular tone, cardiac work, and exerts cardioprotection. This has led to an explosion of papers in which the role of hydrogen sulfide generated in vitro has been used to stimulate biological responses, and where a variety of methods have been used to measure t...
Source: Free Radical Biology and Medicine - September 17, 2009 Category: Biology Authors: Hughes MN, Centelles MN, Moore KP Tags: Free Radic Biol Med Source Type: journals

Antioxidants change platelet responses to various stimulating events.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The platelet role in haemostasis may be influenced by alteration of the platelet redox state - the presence of antioxidants and the formation of reactive oxygen and nitrogen species. We investigated the effects of two antioxidants, resveratrol and trolox, on platelet activation. Trolox and resveratrol inhibited aggregation of washed platelets and platelet rich plasma activated by ADP, collagen and thrombin receptor activating peptide. Resveratrol was a more effective agent in reducing platelet static and dynamic adhesion in comparison with trolox. The antioxidant capacity of resveratrol was, however, the same as that o...
Source: Free Radical Biology and Medicine - September 16, 2009 Category: Biology Authors: Sobotková A, Mášová-Chrastinová L, Suttnar J, Stikarová J, Májek P, Reicheltová Z, Kotlín R, Weisel JW, Malý M, Dyr JE Tags: Free Radic Biol Med Source Type: journals

Physical and functional interactions of Cyclophilin B with neuronal actin and peroxiredoxin-1 are modified by oxidative stress.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Presynaptic actin was identified as a new Torpedo cyclophilin B partner captured in pull-down experiments and by co-immunoprecipitaion The cyclophilin B-actin pull-down interaction was insensitive to the blockade of peptidyl cis/trans prolyl isomerase and calcineurin activities and to the Latrunculin A- and Jasplakinolide-mediated perturbation of F-actin polymerization. Conversely, it was reduced by ATP, and stimulated by a low Cu(2+)- treatment of synaptosomes and by acrolydan-conjugated cyclophilin B. This Cu(2+)-induced stress, in parallel, stimulates the formation of GSH adducts with cysteines of synaptosomal actin...
Source: Free Radical Biology and Medicine - September 16, 2009 Category: Biology Authors: Morot-Gaudry-Talarmain Y Tags: Free Radic Biol Med Source Type: journals

Human-specific Induction of Glutathione Peroxidase-3 by Proteasome Inhibition in Cardiovascular Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Glutathione peroxidase-3 (GPx-3) is a key antioxidant enzyme in the plasma. GPx-3 was previously identified as the major anti-oxidative enzyme to be induced upon nontoxic proteasome inhibition in endothelial cells. Here, we investigated the determinants of proteasome inhibitor-induced expression of GPx-3. Non-toxic proteasome inhibition massively upregulates GPx-3 RNA and protein in human umbilical cord vein cells within 24 hours. Surprisingly, induction of GPx-3 was species-specific for human cells. Exponential upregulation of GPx-3 is mediated by transcriptional activation of the human GPx-3 promoter and in addition ...
Source: Free Radical Biology and Medicine - September 16, 2009 Category: Biology Authors: Westphal K, Stangl V, Fähling M, Dreger H, Weller A, Baumann G, Stangl K, Meiners S Tags: Free Radic Biol Med Source Type: journals