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 'Biological Chemistry' source. Fri, 27 Jan 2012 13:19:52 +0100 http://www.medworm.com/index.php?rid=5374303&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.192 Biological Chemistry 392 (12): 1167-1172 Abstract Cathepsin W is exclusively expressed in immune cells, and a novel isoform was identified previously. To characterize the expression pattern of the wildtype and isoform Ins10, specific polymerase chain reaction assays were generated and used to study respective transcript levels in peripheral blood cells and gastric biopsies in healthy subjects. The wildtype-encoding transcript levels were 3- and 9-fold higher in mucosal samples and peripheral immune cells, respectively (p (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5374303 Fri, 04 Nov 2011 16:47:06 +0100 5374303 http://www.medworm.com/index.php?rid=5374302&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.199 Biological Chemistry 392 (12): 1155-1165 Abstract Ammonia is a major player in the pathogenesis of hepatic encephalopathy (HE) and affects astrocyte function by triggering a self-amplifying cycle between osmotic and oxidative stress. We recently demonstrated that hypoosmotic astrocyte swelling rapidly stimulates nitric oxide (NO) production and increases intracellular free Zn2+ concentration ([Zn2+]i). Here we report effects of ammonia on [Zn2+]i homeostasis and NO synthesis. In cultured rat astrocytes, NH4Cl (5 mm) increased within 6 h both cytosolic and mitochondrial [Zn2+]. The [Zn2+]i increase was transient and was mimicked by the nonmetabolizable CH3NH3Cl, and it was dependent on NO formation, as evidenced by the sensitivity toward the nitric oxide synthase inhibitor NG-monomethyl-l-a... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5374302 Fri, 04 Nov 2011 16:47:06 +0100 5374302 http://www.medworm.com/index.php?rid=5374301&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.187 Biological Chemistry 392 (12): 1145-1154 Abstract The use of recombinant bovine growth hormone (rbGH) to increase milk yield in cows is banned in some countries. In others, where it is authorised, it has triggered harsh debates on labelling of dairy products. If many studies have been performed on bovines, there is a lack of information on buffaloes, which are sometimes treated with rbGH and re­present an important economical resource for dairy products in some countries. Analytical methods with legal value for surveillance of rbGH treatments do not yet exist. Research on gene expression biomarkers is one of the most promising approaches to this purpose. For this reason, we treated five buffaloes for 10 weeks with a sustained-release formulation of rbGH and analysed the response of 20 som... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5374301 Fri, 04 Nov 2011 16:47:06 +0100 5374301 http://www.medworm.com/index.php?rid=5374300&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.174 Biological Chemistry 392 (12): 1135-1144 Abstract PB1-F2 is a nonstructural protein of influenza viruses encoded by the PB1 gene segment from a +1 open reading frame. It has been shown that PB1-F2 contributes to viral pathogenicity, although the underlying mechanisms are still unclear. Induction of type I interferon (IFN) and the innate immune response are the first line of defense against viral infection. Here we show that influenza A viruses (IAVs) lacking the PB1-F2 protein induce an enhanced expression of IFN-β and IFN-stimulated genes in infected epithelial cells. Studying molecular mechanisms underlying the PB1-F2-mediated IFN antagonistic activity showed that PB1-F2 interferes with the RIG-I/MAVS protein complex thereby inhibiting the activation of the downstream transcription fact... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5374300 Fri, 04 Nov 2011 16:47:06 +0100 5374300 http://www.medworm.com/index.php?rid=5374299&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.171 Biological Chemistry 392 (12): 1123-1134 Abstract Inflammation is the biological response to injurious stimuli. In the initial phase of the inflammatory process, interleukin-6 (IL-6) is the main inducer of acute phase protein expression in the liver. A prolonged acute phase response is characterised by a disturbed glucose homeostasis and elevated levels of IL-6, insulin, and counterregulatory hormones such as glucagon. Several studies deal with the impact of IL-6 on glucagon-dependent gene expression. In contrast, only very little is known about the influence of G-protein-coupled receptors on IL-6 signalling. Therefore, the aim of this study is to elucidate the regulation of IL-6-induced gene expression by glucagon. We could reveal a novel mechanism of negative regulation of IL-6-induced M... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5374299 Fri, 04 Nov 2011 16:47:06 +0100 5374299 http://www.medworm.com/index.php?rid=5374298&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.222 Biological Chemistry 392 (12): 1113-1122 Abstract Trypanothione synthetase, a validated drug target, synthesizes trypanothione from glutathione and spermidine. Here we report the gene cloning, expression, characterization and inhibition studies of trypanothione synthetase from Leishmania donovani (LdTryS). The purified recombinant LdTryS enzyme obeyed Michaelis-Menten kinetics. High substrate inhibition was observed with glutathione (Km=33.24 μm, kcat=1.3 s-1, Ki=866 μm). The enzyme shows simple hyperbolic kinetics with fixed glutathione concentration and with other substrates limiting Km values for Mg. ATP and spermidine of 14.2 μm and 139.6 μm, respectively. LdTryS was also screened for inhibitors. Tomatine, conessine, uvaol and betulin were identified as inhibitors of the enzyme and... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5374298 Fri, 04 Nov 2011 16:47:06 +0100 5374298 http://www.medworm.com/index.php?rid=5374297&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.200 Biological Chemistry 392 (12): 1097-1111 Abstract Human 5-lipoxygenase (5-LO) can form dimers as shown here via native gel electrophoresis, gel filtration chromatography and LILBID (laser induced liquid bead ion desorption) mass spectrometry. After glutathionylation of 5-LO by diamide/glutathione treatment, dimeric 5-LO was no longer detectable and 5-LO almost exclusively exists in the monomeric form which showed full catalytic activity. Incubation of 5-LO with diamide alone led to a disulfide-bridged dimer and to oligomer formation which displays a strongly reduced catalytic activity. The bioinformatic analysis of the 5-LO surface for putative protein-protein interaction domains and molecular modeling of the dimer interface suggests a head to tail orientation of the dimer which also expla... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5374297 Fri, 04 Nov 2011 16:47:06 +0100 5374297 http://www.medworm.com/index.php?rid=5374296&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.194 Biological Chemistry 392 (12): 1089-1095 Abstract Human UDP glycosyltransferases (UGTs) play an important role in xenobiotic detoxification. They increase the solubility of their substrates by adding a sugar moiety (such as glucuronic acid) to different functional entities (such as hydroxyl groups). The aim of this study was to investigate how glucuronidation of a standard substrate is affected by a change of the hetero­atom at the conjugation site. For this purpose, we compared the in vitro glucuronidation rates of 4-methylumbelliferone and 7-mercapto-4-methylcoumarin, respectively. Human liver microsomes catalyzed the S-glucuronidation of 7-mercapto-4-­methylcoumarin almost as efficient as the O-glucuronidation of 4-methylumbelliferone. When testing isoenzyme specificity by whole cell ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5374296 Fri, 04 Nov 2011 16:47:06 +0100 5374296 http://www.medworm.com/index.php?rid=5374295&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.208 Biological Chemistry 392 (12): 1077-1088 Abstract Group A streptococcus (Streptococcus pyogenes) is an exclusively human pathogen that causes a wide spectrum of diseases ranging from pharyngitis, to impetigo, to toxic shock, to necrotizing fasciitis. The diversity of these disease states necessitates that S. pyogenes possess the ability to modulate both the innate and adaptive immune responses. SpeB, a cysteine proteinase, is the predominant secreted protein from S. pyogenes. Because of its relatively indiscriminant specificity, this enzyme has been shown to degrade the extracellular matrix, cytokines, chemokines, complement components, immunoglobulins, and serum protease inhibitors, to name but a few of the known substrates. Additionally, SpeB regulates other streptococcal proteins by deg... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5374295 Fri, 04 Nov 2011 16:47:06 +0100 5374295 http://www.medworm.com/index.php?rid=5374294&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.195 Biological Chemistry 392 (12): 1053-1075 Abstract Squalene monooxygenase catalyzes the epoxidation of C-C double bond of squalene to yield 2,3-oxidosqualene, the key step of sterol biosynthesis pathways in eukaryotes. Sterols are essential compounds of these organisms and squalene epoxidation is an important regulatory point in their synthesis. Squalene monooxygenase downregulation in vertebrates and fungi decreases synthesis of cholesterol and ergosterol, respectively, which makes squalene monooxygenase a potent and attractive target of hypercholesterolemia and antifungal therapies. Currently some fungal squalene monooxygenase inhibitors (terbinafine, naftifine, butenafine) are in clinical use, whereas mammalian enzymes’ inhibitors are still under investigation. Research on new squalene... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5374294 Fri, 04 Nov 2011 16:47:06 +0100 5374294 http://www.medworm.com/index.php?rid=5292419&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.166 Biological Chemistry 392 (11): 1047-1051 Abstract High tumor tissue mRNA expression of the tumor biological factors uPAR, uPAR-del4/5, or rab31 is associated with shorter distant metastasis-free and overall survival in breast cancer patients. To evaluate whether these factors are also clinically relevant in ovarian cancer, we quantified the respective mRNA levels in primary tumor tissue of advanced ovarian cancer patients (n=103) and evaluated their association with clinicopathological parameters and patients’ prognosis. mRNA expression levels of all three markers did not show any significant association with overall or progression-free survival, demonstrating that these factors have no prognostic value in advanced ovarian cancer. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5292419 Fri, 07 Oct 2011 06:00:14 +0100 5292419 http://www.medworm.com/index.php?rid=5292418&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.099 Biological Chemistry 392 (11): 1039-1045 Abstract Bacterial collagenases exhibit a multimodular domain organization. While the N-terminal collagenase unit harbors the catalytic zinc and suffices to degrade peptidic substrates, collagen substrates come in different types, explaining the requirement for accessory domains such as polycystic kidney disease (PKD)-like domains for efficient catalysis. How the recognition and unfolding of (micro-)fibrillar or triple-helical collagen is accomplished are only poorly understood. Here, we present the crystal structure of the PKD-like domain of collagenase G from Clostridium histolyticum. The β-barrel structure reveals a two-tier architecture, connected by kinked hinge segments. Together with sheet extension as a generic oligomerization mechanism, th... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5292418 Fri, 07 Oct 2011 06:00:14 +0100 5292418 http://www.medworm.com/index.php?rid=5292417&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.158 Biological Chemistry 392 (11): 1031-1037 Abstract Proteomic identification of protease cleavage site specificity (PICS) is a recent proteomic approach for the easy mapping of protease subsite preferences that determines both the prime- and non-prime side specificity concurrently. Here we greatly facilitate user access by providing an automated and simple web-based data-analysis resource termed WebPics (http://clipserve.clip.ubc.ca/pics/). We demonstrate the utility of WebPics analysis of PICS data by determining the substrate specificity of factor Xa from P6-P6’, an important blood coagulation protease that proteolytically generates thrombin from prothrombin. PICS confirms existing data on non-prime site specificity and refines our knowledge of factor Xa prime-site selectivity. (Source: ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5292417 Fri, 07 Oct 2011 06:00:14 +0100 5292417 http://www.medworm.com/index.php?rid=5292416&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.095 Biological Chemistry 392 (11): 1021-1029 Abstract The bradykinin (BK) B2 and B1 receptors (B2R, B1R) belong to the rhodopsin-like G protein-coupled receptors (GPCRs) and are involved in (patho)physiological processes such as blood pressure regulation or inflammation. They mediate the effects of the pro-inflammatory peptides bradykinin/kallidin and desArg9-BK/desArg10-kallidin, respectively. Whereas the B2R is constitutively expressed and gets internalized upon activation, the B1R is especially induced by inflammatory mediators and responds to stimulation with increased surface receptor numbers. Stimulation of both receptors activates phospholipase Cβ (PLCβ) and mitogen activated protein kinase (MAPK) signaling. Because inflammatory processes are characterized by heat (fever), we analyzed... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5292416 Fri, 07 Oct 2011 06:00:14 +0100 5292416 http://www.medworm.com/index.php?rid=5292415&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.164 Biological Chemistry 392 (11): 1011-1020 Abstract WNT/Frizzled receptor (FZD) signaling pathways are pivotal for physiological and pathophysiological processes. In humans, the complexity of WNT/FZD signaling is based on 19 WNTs, 10 FZDs and at least two (co)receptors (LRP5/6) mediating supposably four different signaling cascades. The detailed investigation of the specific function of the different initiating components is primarily hampered by the lack of most WNT proteins in a purified form. Therefore, we constructed and examined a chimeric protein of WNT3a and FZD4 as a suitable approach to overcome this obstacle for future studies of the specificity of other WNT/FZD combinations. Furthermore, we produced four different reporter HEK 293 cell lines to quantify the induced activation of t... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5292415 Fri, 07 Oct 2011 06:00:14 +0100 5292415 http://www.medworm.com/index.php?rid=5292414&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.165 This study suggests that substituents other than P1′ and P2′ may confer selectivity among MMPs and may aid in the search for novel lead compounds. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5292414 Fri, 07 Oct 2011 06:00:14 +0100 5292414 http://www.medworm.com/index.php?rid=5292413&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.169 Biological Chemistry 392 (11): 995-1001 Abstract Nicastrin is a type I transmembrane glycoprotein, which is part of the high molecular weight γ-secretase complex. γ-Secretase is one of the key players associated with the generation of Alzheimer's disease pathology, since it liberates the neurotoxic amyloid β-peptide. Four proteins Nicastrin, anterior pharynx-defective-1 (Aph-1), presenilin enhancer-2 (Pen-2) and Presenilin are essential to form the active γ-secretase complex. Recently it has been shown, that Nicastrin has a key function in stabilizing the mature γ-secretase complex and may also be involved in substrate recognition. So far no structural data for the Nicastrin ectodomain or any other γ-secretase component are available. We therefore used Circular Dichroism (CD) spectro... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5292413 Fri, 07 Oct 2011 06:00:14 +0100 5292413 http://www.medworm.com/index.php?rid=5292412&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.096 In this study an analog approach was used to express chi-meric cathepsin B specifically in the intestine of transgenic animals. No overt phenotype was observed for the transgenic mice that reproduced normally. Biochemical and morphological studies confirmed that the overall intestinal phenotype including the structure and polarity of this tissue as well as cell numbers and differentiation states were not altered in the A33-CathB-EGFP mice when compared to wild type animals. However, transgenic expression of chimeric cathepsin B could not be visualized because it was not translated in situ although the transgene was maintained over several generations. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5292412 Fri, 07 Oct 2011 06:00:14 +0100 5292412 http://www.medworm.com/index.php?rid=5292411&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.100 Biological Chemistry 392 (11): 973-981 Abstract In eucaryotes, many secreted proteins and peptides are proteolytically excised from larger precursor proteins by a specific class of serine proteases, the proprotein/prohormone convertases (PCs). This cleavage is essential for substrate activation, making the PCs very interesting pharmacological targets in cancer and infectious disease research. Correspondingly, their structure, function and inhibition are intensely studied – studies that require the respective target proteins in large amounts and at high purity. Here we describe the development of a novel purification protocol of furin, the best-studied member of the PC family. We combined the heterologous expression of furin from CHO cells with a novel purification scheme employing an aff... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5292411 Fri, 07 Oct 2011 06:00:14 +0100 5292411 http://www.medworm.com/index.php?rid=5292410&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.162 Biological Chemistry 392 (11): 961-971 Abstract The endolysosomal cysteine endoprotease cathepsin L is secreted from cells in a variety of pathological conditions such as cancer and arthritis. We compared the secretome composition and extracellular proteolytic cleavage events in cell supernatants of cathepsin L-deficient and wild-type mouse embryonic fibroblasts (MEFs). Quantitative proteomic comparison of cell conditioned media indicated that cathepsin L deficiency affects, albeit in a limited manner, the abundances of extracellular matrix (ECM) components, signaling proteins, and further proteases as well as endogenous protease inhibitors. Immunodetection corroborated that cathepsin L deficiency results in decreased abundance of the ECM protein periostin and elevated abundance of matrix ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5292410 Fri, 07 Oct 2011 06:00:14 +0100 5292410 http://www.medworm.com/index.php?rid=5292409&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.185 Biological Chemistry 392 (11): 955-960 Abstract The development of new and effective drug delivery systems for cancer treatment represents one of the significant challenges facing biomedical technology in the last decade. Among the different methods of drug delivery, magnetic drug targeting, by enabling specific delivery of chemotherapeutic agents through the use of magnetic nanoparticles and magnetic field gradient, could be a promising approach. Recently, magnetic nanoparticles have attracted additional attention because of their potential as contrast agents for magnetic resonance imaging and heat mediators for cancer therapy. This review summarizes these approaches in the use of magnetic nanoparticles in biomedical applications and novel methods for their optimization. (Source: Biologic... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5292409 Fri, 07 Oct 2011 06:00:14 +0100 5292409 http://www.medworm.com/index.php?rid=5292408&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.092 Biological Chemistry 392 (11): 949-954 Abstract Proteases are pivotal modulators of extracellular matrix components and bioactive proteins at all phases of cutaneous wound healing and thereby essentially contribute to the successful reestablishment of skin integrity upon injury. As a consequence, disturbance of proteolytic activity at the wound site is a major factor in the pathology of chronic wounds. A large body of data acquired in many years of research provide a good understanding of how individual proteases may influence the repair process. The next challenge will be to integrate these findings and to elucidate the complex interactions of proteolytic enzymes, their inhibitors and substrates on a system-wide level. Here, we present novel approaches that might help to achieve this ambi... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5292408 Fri, 07 Oct 2011 06:00:14 +0100 5292408 http://www.medworm.com/index.php?rid=5292407&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.214 Biological Chemistry 392 (11): 947-947 No abstract available (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5292407 Fri, 07 Oct 2011 06:00:14 +0100 5292407 http://www.medworm.com/index.php?rid=5203581&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.097 In this study, we analysed the autoproteolytic active domain of zucchini yellow mosaic virus (ZYMV) HC-Pro. Several Escherichia coli-expressed MBP:HC-Pro:GFP mutants containing deletions or point mutations at either the N- or C-terminus of the HC-Pro protein were examined. Our results showed that amino acids essential for the proteolytic activity of ZYMV HC-Pro are distinct from those of the tobacco etch virus HC-Pro, although the amino acid sequences in the proteolytic active domain are conserved among potyviruses. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5203581 Sun, 11 Sep 2011 02:46:00 +0100 5203581 http://www.medworm.com/index.php?rid=5203580&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.076 In this study, we examined trans-endoproteolytic cleavage activities of membrane-anchored and replicase-associated NS3-4A using an internally consistent set of membrane-anchored protein substrates mimicking all known HCV NS3-4A polyprotein cleavage sequences. Interestingly, we detected cleavage of substrates encoding for the NS4B/NS5A and NS5A/NS5B junctions, but not for the NS3/NS4A and NS4A/NS4B substrates. This stringent substrate recognition profile was also observed for the replicase-associated NS3-4A and is not genotype-specific. Our study also reveals that ER-anchoring of the substrate is critical for its cleavage by NS3-4A. Importantly, we demonstrate that in HCV-infected cells, the NS4B/NS5A substrate was cleaved efficiently. The unique ability of our membrane-anchored substrates ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5203580 Sun, 11 Sep 2011 02:46:00 +0100 5203580 http://www.medworm.com/index.php?rid=5203579&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.084 Biological Chemistry 392 (10): 919-926 Abstract Amyloid plaques consisting of aggregated Aβ peptide are a hallmark of Alzheimer's disease. Among the different forms of Aβ, the one of 42aa length (Aβ42) is most aggregation-prone and also the most neurotoxic. We find that eye-specific expression of human Aβ42 in Drosophila results in a degeneration of eye structures that progresses with age. Dietary supplements of zinc or copper ions exacerbate eye damage. Positive effects are seen with zinc/copper chelators, or with elevated expression of MTF-1, a transcription factor with a key role in metal homeostasis and detoxification, or with human or fly transgenes encoding metallothioneins, metal scavenger proteins. These results show that a tight control of zinc and copper availability can mini... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5203579 Sun, 11 Sep 2011 02:46:00 +0100 5203579 http://www.medworm.com/index.php?rid=5203578&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.176 Biological Chemistry 392 (10): 909-918 Abstract Effects of insulin excess and deficiency on glucose-dependent insulinotropic polypeptide (GIP) was examined in rats following insulinoma transplantation or streptozotocin (STZ) administration. Over 14 days, food intake was increased (p (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5203578 Sun, 11 Sep 2011 02:46:00 +0100 5203578 http://www.medworm.com/index.php?rid=5203577&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.087 Biological Chemistry 392 (10): 897-908 Abstract It has been reported that the arylhydrocarbon receptor (AHR) is overexpressed in certain types of breast tumors. However, so far no concrete evidence has been provided yet as to why and how the overexpressed AHR in those cancer cells is functionally activated without exogenous ligands. Here we show that the AHR was functionally activated when estrogen receptor-negative, AHR overexpressing MCF10AT1 human breast cancer cells (designated P20E) were subjected to serum starvation. Transfection of cells with ETK-KQ, a plasmid for kinase-dead epithelial and endothelial tyrosine kinase (ETK), attenuated this AHR activation. Artificial over-expression of ETK in P20E cells through transfection with wild-type ETK plasmid (ETK-wt) caused up-regulation of... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5203577 Sun, 11 Sep 2011 02:46:00 +0100 5203577 http://www.medworm.com/index.php?rid=5203576&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.085 Biological Chemistry 392 (10): 887-895 Abstract Genetic modification of human embryonic stem cells (hESCs) using biophysical DNA transfection methods are hampered by the very low single cell survival rate and cloning efficiency of hESCs. Lentiviral gene transfer strategies are widely used to genetically modify hESCs but limited transduction efficiencies in the presence of feeder or stroma cells present problems, particularly if vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped viral particles are applied. Here, we investigated whether the recently described semen derived enhancer of virus infection (SEVI) and alternative viral envelope proteins derived from either Gibbon ape leukaemia virus (GALV) or feline leukaemia virus (RD114) are applicable for transducing hESCs during co-cu... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5203576 Sun, 11 Sep 2011 02:46:00 +0100 5203576 http://www.medworm.com/index.php?rid=5203575&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.080 This study indicates that ADAM15 is required for normal skeletal homeostasis and that its absence causes increased nuclear translocation of β-catenin in osteoblasts leading to increased osteoblast proliferation and function, which results in higher trabecular and cortical bone mass. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5203575 Sun, 11 Sep 2011 02:46:00 +0100 5203575 http://www.medworm.com/index.php?rid=5203574&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.098 In this study, we investigated the effects of influenza A virus lung infection on the expression of SULTs in the lung, brain, and liver of female C57BL/6 mice. Our results demonstrate for the first time that SULT2B1b enzyme activity and protein expression are significantly up-regulated in the lung and brain of female mice in response to lung influenza A virus infection. Real-time quantitative PCR results are consistent with Western blot and enzymatic activity data. In mouse liver, mSULT2B1b is not significantly changed. Enzyme activities, protein expression, and mRNA expression of SULT1A1 and SULT2A1 in the lung, brain, and liver of mice were not significantly affected by the infection. The induction of SULT2B1b may be used to inactivate natural liver X receptor ligands and activate the pr... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5203574 Sun, 11 Sep 2011 02:46:00 +0100 5203574 http://www.medworm.com/index.php?rid=5203573&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.173 Biological Chemistry 392 (10): 859-867 Abstract The mechanisms of oxidation of low-density lipoproteins (LDLs) are not well defined, but epidemiological and experimental studies suggest that iron-catalyzed processes may contribute to atherogenesis. The aim of this study was to test the hypothesis that iron-catalyzed oxidations of LDLs in vitro produce diagnostic biomarkers of oxidation of the apolipoprotein that could be applied to studies in vivo. LDLs were oxidized in the presence of Fe2+, EDTA, and ascorbic acid for up to 40 h. Following delipidation and trypsin digestion, the peptides were separated by HPLC, with four peaks detected at 365 nm, whereas none were observed in peptides from unoxidized LDLs. The peptides were identified by MALDI-QTOF mass spectrometry as IVQILP(W+4) EQNEQ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5203573 Sun, 11 Sep 2011 02:46:00 +0100 5203573 http://www.medworm.com/index.php?rid=5203572&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.151 Biological Chemistry 392 (10): 849-858 Abstract SecB is a homotetrameric cytosolic chaperone that forms part of the protein translocation machinery in E. coli. Due to SecB, nascent polypeptides are maintained in an unfolded translocation-competent state devoid of tertiary structure and thus are guided to the translocon. In vitro SecB rapidly binds to a variety of ligands in a non-native state. We have previously investigated the bound state conformation of the model substrate bovine pancreatic trypsin inhibitor (BPTI) as well as the conformation of SecB itself by using proximity relationships based on site-directed spin labeling and pyrene fluorescence methods. It was shown that SecB undergoes a conformational change during the process of substrate binding. Here, we generated SecB mutants ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5203572 Sun, 11 Sep 2011 02:46:00 +0100 5203572 http://www.medworm.com/index.php?rid=5203571&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.121 Biological Chemistry 392 (10): 837-847 Abstract Influenza is still one of the major plagues worldwide with the threatening potential to cause pandemics. In recent years, increasing levels of resistance to the four FDA approved anti-influenza virus drugs have been described. This situation underlines the urgent need for novel anti-virals in preparation for future influenza epidemics or pandemics. Although the anti-virals currently in use target viral factors such as the neuraminidase or the M2 ion channel, there is an increase in pre-clinical approaches that focus on cellular factors or pathways that directly or indirectly interact with virus replication. This does not only include inhibitors of virus-supportive signaling cascades but also interaction blockers of viral proteins with host ce... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5203571 Sun, 11 Sep 2011 02:46:00 +0100 5203571 http://www.medworm.com/index.php?rid=5116628&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.078 Biological Chemistry 392 (8-9): 831-835 Abstract Many pathogens have evolved a variety of mechanisms to exploit the host-cell actin cytoskeleton during infection, either to enter into cells or to move within cells. These events have been investigated and documented in detail. Yet, a complete picture of the molecules and mechanisms regulating entry and intracellular movement remains to be established. Here we present a series of studies revealing that in addition to actin rearrangements the host cell also employs septins, a relatively newly characterized component of the cell cyto-skeleton, to regulate bacterial entry and restrict the dissemination of cytosolic bacteria. The challenge now is to decipher the precise role of septins during actin rearrangements and how these different cytoskel... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5116628 Thu, 11 Aug 2011 16:35:35 +0100 5116628 http://www.medworm.com/index.php?rid=5116627&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.083 Biological Chemistry 392 (8-9): 813-829 Abstract Septins are essential for cytokinesis in Saccharomyces cerevisiae, but their precise roles remain elusive. Currently, it is thought that before cytokinesis, the hourglass-shaped septin structure at the mother-bud neck acts as a scaffold for assembly of the actomyosin ring (AMR) and other cytokinesis factors. At the onset of cytokinesis, the septin hourglass splits to form a double ring that sandwiches the AMR and may function as diffusion barriers to restrict diffusible cytokinesis factors to the division site. Here, we show that in cells lacking the septin Cdc10 or the septin-associated protein Bud4, the septins form a ring-like structure at the mother-bud neck that fails to re-arrange into a double ring early in cytokinesis. Strikingly, AM... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5116627 Thu, 11 Aug 2011 16:35:35 +0100 5116627 http://www.medworm.com/index.php?rid=5116626&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.090 Biological Chemistry 392 (8-9): 805-812 Abstract During asymmetric cell division, spindle positioning is critical for ensuring the unequal inheritance of polarity factors. In budding yeast, the mother-bud neck determines the cleavage plane and a correct nuclear division between mother and daughter cell requires orientation of the mitotic spindle along the mother-bud axis. A surveillance device called the spindle position/orientation checkpoint (SPOC) oversees this process and delays mitotic exit and cytokinesis until the spindle is properly oriented along the division axis, thus ensuring genome stability. Cytoskeletal proteins called septins form a ring at the bud neck that is essential for cytokinesis. Furthermore, septins and septin-associated proteins are implicated in spindle positioni... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5116626 Thu, 11 Aug 2011 16:35:35 +0100 5116626 http://www.medworm.com/index.php?rid=5116625&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.074 Biological Chemistry 392 (8-9): 799-803 Abstract The annulus is an electron-dense ring structure connecting the midpiece and the principal piece of the mammalian sperm flagellum. Proteins from the septin family have been shown to localize to the annulus. A septin complex is assembled early in spermiogenesis with the cochaperone DNAJB13 and, in mature sperm, associates with Testis Anion Transporter 1; SLC26A8 (Tat1), a transmembrane protein of the SLC26 family. Studies in mice have shown that the annulus acts as a barrier to protein diffusion and controls correct organization of the midpiece. Consistent with these findings, absence of the annulus is associated with flagellum differentiation defects and asthenozoospermia in humans. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5116625 Thu, 11 Aug 2011 16:35:35 +0100 5116625 http://www.medworm.com/index.php?rid=5116624&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.082 Biological Chemistry 392 (8-9): 791-797 Abstract Septins constitute a family of conserved guanine nucleotide binding proteins found in a wide range of organisms from fungi to mammals. Members of the family share a canonical G-domain with N- and C-terminal extensions. G-domains assemble into hetero-oligomeric complexes which form non-polarised filaments or rings. Linear filaments are formed between the G-domains using either the guanine nucleotide binding site (G interface) or N- and C-terminal extensions (NC interface). Sept7 is a unique among the 13 human septins in that it occupies the ends of hexameric building blocks which assemble into non-polarised filaments. To gain insight into its particular properties we performed structural and biochemical studies on Sept7. We solved the crystal... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5116624 Thu, 11 Aug 2011 16:35:35 +0100 5116624 http://www.medworm.com/index.php?rid=5116623&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.089 Biological Chemistry 392 (8-9): 783-790 Abstract The human Septin 4 gene (Sept4) encodes two major protein isoforms; Sept4_i1 (H5/PNUTL2) and Sept4_i2/ARTS. Septins have been traditionally studied for their role in cytokinesis and their filament-forming abilities, but subsequently have been implicated in diverse functions, including membrane dynamics, cytoskeletal reorganization, vesicle trafficking, and tumorigenesis. ARTS is localized at mitochondria and promotes programmed cell death (apoptosis). These features distinguish ARTS from any other known human septin family member. This review compares the structural and functional properties of ARTS with other septins. In addition, it describes how a combination of two distinct promoters, differential splicing, and intron retention leads to ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5116623 Thu, 11 Aug 2011 16:35:35 +0100 5116623 http://www.medworm.com/index.php?rid=5116622&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.093 Biological Chemistry 392 (8-9): 779-781 Abstract Septins are cytoskeletal GTP-binding proteins involved in processes characterized by active membrane movement, such as cytokinesis, vesicle trafficking and exocytosis. Most septins are expressed ubiquitously, however, some septins accumulate in particular tissues. The ubiquitous SEPT11 also shows high expression levels in the central nervous system and in platelets. Here, SEPT11 is involved in vesicle trafficking and may play a role in synaptic connectivity. Interestingly, mice that harbor a homozygous Sept11 null mutation, die in utero. From day 11.5 post coitum onwards, development of homozygous embryos seems to be retarded and the embryos from day 13.5 onwards were dead. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5116622 Thu, 11 Aug 2011 16:35:35 +0100 5116622 http://www.medworm.com/index.php?rid=5116621&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.088 Biological Chemistry 392 (8-9): 769-777 Abstract Septin9 (Sept9) is a member of the filament-forming septin family of structural proteins and is associated with a variety of cancers and with hereditary neuralgic amyotrophy. We have generated mice with constitutive and conditional Sept9 knockout alleles. Homozygous deletion of Sept9 results in embryonic lethality around day 10 of gestation whereas mice homozygous for the conditional allele develop normally. Here we report the consequences of homozygous loss of Sept9 in immortalized murine embryonic fibroblasts. Proliferation rate was not changed but cells without Sept9 had an altered morphology compared to normal cells, particularly under low serum stress. Abnormal, fragmented, and multiple nuclei were more frequent in cells without Sept9. ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5116621 Thu, 11 Aug 2011 16:35:35 +0100 5116621 http://www.medworm.com/index.php?rid=5116620&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.079 Biological Chemistry 392 (8-9): 763-767 Abstract The human septins are part of a gene family, that is a group of genes with similar sequences and usually but not invariably share similar functions that are descended from a common ancestor. Here we review our current knowledge of the human septin gene family and highlight areas of uncertainty. Currently 13 human septin genes are known (SEPT1 to SEPT12 and SEPT14). What was known as SEPT13 is now defined as one of many SEPT7 related pseudogenes. The family is characterized by complex genomics and extensive (but not universal) splicing, giving rise to a plethora of septin isoforms. For only a few members of the family do we have a comprehensive insight into these transcripts and isoforms. Given the formation of countless septin homotypic and ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5116620 Thu, 11 Aug 2011 16:35:35 +0100 5116620 http://www.medworm.com/index.php?rid=5116619&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.081 In this study, we extensively characterized septin interaction partners using yeast two-hybrid and three-hybrid systems in addition to precipitation analyses in platelets. As a result, we identified human hetero-trimeric septin complexes on a large scale, which had been only postulated in the past. In addition, we illustrated roles of SEPT9 that might contribute to hetero-trimeric septin complex formation. SEPT9 can substitute for septins of the SEPT2 group and partially for SEPT7. Mutagenic analyses revealed that mutation of a potential phosphorylation site in SEPT7 (Y318) regulates the interaction with other septins. We identified several septin-septin interactions in platelets suggesting a regulatory role of diverse septin complexes in platelet function. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5116619 Thu, 11 Aug 2011 16:35:35 +0100 5116619 http://www.medworm.com/index.php?rid=5116618&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.077 Biological Chemistry 392 (8-9): 739-749 Abstract Septins are GTPases that form heteromeric complexes and are linked to neurological disorders. Although several septin subcomplexes have been reported in various mammalian tissues, the cellular and subcellular distribution of these complexes is largely unexplored. Using antibodies against ten mammalian septins, we show that septins diverge with respect to their tissue distribution implying that septin complexes in various tissues have unique composition. Although all ten septins examined were expressed in brain tissue, we describe septin complex(es) including SEPT3, SEPT5, SEPT6, SEPT7 and SEPT11 that could be functional within the presynapse because, unlike other septins they: (1) showed an increase in expression from embryonic day 15 to pos... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5116618 Thu, 11 Aug 2011 16:35:35 +0100 5116618 http://www.medworm.com/index.php?rid=5116617&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.073 Biological Chemistry 392 (8-9): 725-738 Abstract Septins are a family of cytoskeleton related proteins consisting of 14 members that associate and interact with actin and tubulin. From yeast to humans, septins maintain a conserved role in cytokinesis and they are also involved in a variety of other cellular functions including chromosome segregation, DNA repair, migration and apoptosis. Tumorigenesis entails major alterations in these processes. A substantial body of literature reveals that septins are overexpressed, downregulated or generate chimeric proteins with MLL in a plethora of solid tumors and in hematological malignancies. Thus, members of this gene family are emerging as key players in tumorigenesis. The analysis of septins during cancer initiation and progression is challenged ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5116617 Thu, 11 Aug 2011 16:35:35 +0100 5116617 http://www.medworm.com/index.php?rid=5116616&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.072 Biological Chemistry 392 (8-9): 713-724 Abstract The mixed lineage leukemia (MLL) locus is involved in more than 60 different rearrangements with a remarkably diverse group of fusion partners in approximately 10% of human leukemias. MLL rearrangements include chromosomal translocations, gene internal duplications, chromosome 11q deletions or inversions and MLL gene insertions into other chromosomes, or vice versa. MLL fusion partners can be classified into four distinct categories: nuclear proteins, cytoplasmatic proteins, histone acetyltransferases and septins. Five different septin genes (SEPT2, SEPT5, SEPT6, SEPT9, and SEPT11) have been identified as MLL fusion partners, giving rise to chimeric fusion proteins in which the N terminus of MLL is fused, in frame, to almost the entire open ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5116616 Thu, 11 Aug 2011 16:35:35 +0100 5116616 http://www.medworm.com/index.php?rid=5116615&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.091 Biological Chemistry 392 (8-9): 699-712 Abstract Membrane trafficking via targeted exocytosis to the Saccharomyces cerevisiae bud neck provides new membrane and membrane-associated factors that are critical for cytokinesis. It remains unknown whether yeast plasma membrane abscission, the final step of cytokinesis, occurs spontaneously following extensive vesicle fusion, as in plant cells, or requires dedicated membrane fission machinery, as in cultured mammalian cells. Components of the endosomal sorting complexes required for transport (ESCRT) pathway, or close relatives thereof, appear to participate in cytokinetic abscission in various cell types, but roles in cell division had not been documented in budding yeast, where ESCRTs were first characterized. By contrast, the septin family of... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5116615 Thu, 11 Aug 2011 16:35:35 +0100 5116615 http://www.medworm.com/index.php?rid=5116614&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.075 Biological Chemistry 392 (8-9): 689-697 Abstract Although the septin ring and collar in budding yeast were described over 20 years ago, there is still controversy regarding the organization of septin filaments within these structures and about the way in which the ring first forms and about how it converts into a collar at the mother-bud neck. Here we present quantitative analyses of the recruitment of fluorescently-tagged septins to the ring and collar through the cell cycle. Septin ring assembly began several minutes after polarity establishment and this interval was longer in daughter than in mother cells, suggesting asymmetric inheritance of septin regulators. Septins formed an initial faint and irregular ring, which became more regular as septins were recruited at a constant rate. Th... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5116614 Thu, 11 Aug 2011 16:35:35 +0100 5116614 http://www.medworm.com/index.php?rid=5116613&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.086 Biological Chemistry 392 (8-9): 681-687 Abstract Until recently, it had appeared that the septin family of proteins was restricted to the opisthokont eukaryotes (the fungi and animals and their close relatives the microsporidia and choanoflagellates). It has now become apparent that septins are also present in several other widely divergent eukaryotic lineages (chlorophyte algae, brown algae, and ciliates). This distribution and the details of the non-opisthokont septin sequences appear to require major revisions to hypotheses about the origins and early evolution of the septins. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5116613 Thu, 11 Aug 2011 16:35:35 +0100 5116613 http://www.medworm.com/index.php?rid=5116612&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.094 Biological Chemistry 392 (8-9): 679-680 No abstract available (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=5116612 Sun, 31 Jul 2011 23:00:00 +0100 5116612 http://www.medworm.com/index.php?rid=4919779&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.068 Biological Chemistry 392 (7): 665-677 Abstract In the present studies we resolved the post-translational microheterogeneity of purified porcine dipeptidyl peptidase IV (DP 4) from kidney cortex. Applying SDS-homogeneous DP 4 onto an analytical agarose isoelectric focusing (IEF) gel, pH 4–6, activity staining resulted in at least 17 isoforms between pH 4.8–6.0. These could be separated into fractions with only two to six isoforms by means of preparative liquid-phase IEF, using a Rotofor cell. Starting off with three parallel Rotofor runs under the same conditions at pH 5–6, the fractions were pooled according to the specific activity of DP 4, pH and analytical IEF profile, and further refractionated without any additional ampholytes. Since excessive dilution of ampholytes and proteins... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4919779 Sat, 11 Jun 2011 01:28:32 +0100 4919779 http://www.medworm.com/index.php?rid=4919778&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.070 Biological Chemistry 392 (7): 653-664 Abstract Over the past years the members of the type II transmembrane serine protease (TTSP) family have emerged as new players in mammalian biology. TMPRSS4 (transmembrane protease/serine) is overexpressed in several human cancer tissues, promoting invasion, migration, and metastasis. However, the physiological function has not yet been elucidated. Here, we present morpholino knockdown studies targeting TMPRSS4a, a homolog of human TMPRSS4 in zebrafish embryos. By RT-PCR, we could demonstrate an expression of this protease already 5 h post-fertilization, suggesting important functions in the early stages of embryonic development. Indeed, in vivo gene silencing caused severe defects in tissue development and cell differentiation including a disturbed ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4919778 Sat, 11 Jun 2011 01:28:32 +0100 4919778 http://www.medworm.com/index.php?rid=4919777&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.067 Biological Chemistry 392 (7): 643-651 Abstract While activation of the aryl hydrocarbon receptor (AhR) by exogenous ligands is well investigated, its physiological function is less understood. By extending research in AhR biology, evidence appeared that the receptor generally plays an important role in cell physiology. In keratinocytes, little is known about endogenous functions of the AhR. In order to expand this knowledge, we analyzed the impact of AhR knockdown on cell cycle progression in HaCaT cells and showed that proliferation of siAhR HaCaT cells was significantly decreased. In line with that result, western blot analysis revealed that protein level of the cyclin dependent kinase inhibitor p27KIP1 was increased, whereas protein level of the cyclin dependent kinase (CDK) 2 was reduc... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4919777 Sat, 11 Jun 2011 01:28:32 +0100 4919777 http://www.medworm.com/index.php?rid=4919776&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.062 Biological Chemistry 392 (7): 633-642 Abstract Pleural inflammation underlies the formation of most exudative pleural effusions and the plasma kallikrein-kinin system (KKS) is known to contribute. Mesothelial cells are the predominant cell type in the pleural cavity, but their potential role in plasma KKS activation and BK production has not been studied. Bradykinin concentrations were higher in pleural fluids than the corresponding serum samples in patients with a variety of diseases. Bradykinin concentrations did not correlate with disease diagnosis, but were elevated in exudative effusions. It was demonstrated, using a range of primary and transformed mesothelial and mesothelioma cell lines, that cells assembled high molecular weight kininogen and plasma prekallikrein to liberate bradyk... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4919776 Sat, 11 Jun 2011 01:28:32 +0100 4919776 http://www.medworm.com/index.php?rid=4919775&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.064 Biological Chemistry 392 (7): 625-632 Abstract Fanconi anemia (FA) is a rare cancer-prone genetic disorder characterized by progressive bone marrow failure, chromosomal instability and redox abnormalities. There is much biochemical and genetic data, which strongly suggest that FA cells experience increased oxidative stress. The present study was designed to elucidate if differences in oxidant state exist between control, idiopathic bone marrow failure (idBMF) and FA cells, and to analyze oxidant state of cells in FA heterozygous carriers as well. The results of the present study confirm an in vivo prooxidant state of FA cells and clearly indicate that FA patients can be distinguished from idBMF patients based on the oxidant state of cells. Female carriers of FA mutation also exhibited hall... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4919775 Sat, 11 Jun 2011 01:28:32 +0100 4919775 http://www.medworm.com/index.php?rid=4919774&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.063 Biological Chemistry 392 (7): 617-624 Abstract General diffusion porins are passive transmembrane channels. We have explored the possibility to create artificial nanopores starting from natural β-barrel structures. Structural elements of bacterial porins were used to build a series of artificial nanopores. The basic module was selected by multi-alignment of general diffusion porins. The sequence corresponded to a highly conserved motif containing two β-strands, which was obtained from Escherichia coli OmpF. Dimeric to octameric repeats were obtained through cDNA recombinant technology. The hexameric repeat was used to test its properties. This protein was expressed, purified and reconstituted in the planar bilayer membranes. It was able to form channels in membranes with a conductance of... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4919774 Sat, 11 Jun 2011 01:28:32 +0100 4919774 http://www.medworm.com/index.php?rid=4919773&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.065 Biological Chemistry 392 (7): 609-616 Abstract To identify the functional gene fragment, a neutrophil inhibitory factor (NIF) like protein was found in the buccal gland of Lampetra japonica, suggesting that this related lamprey protein represents a novel class of integrin receptor antagonists. The recombinant Lampetra japonica-NIF like (rLj-NIF) was identified by SDS-PAGE and purified by using His·Bind affinity chromatography. Effect of rLj-NIF on neutrophil migration suggested that rLj-NIF can act as a neutrophil inhibitory factor. Besides that, oxidative burst activity of neutriphil was tested by flow cytometry using dihydrorhodamine (DHR123) as a fluorogenic substrate, and the data suggested that the mean fluorescence intensity significantly decreased compared with positive controls (p... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4919773 Sat, 11 Jun 2011 01:28:32 +0100 4919773 http://www.medworm.com/index.php?rid=4919772&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.066 Biological Chemistry 392 (7): 601-608 Abstract TPR proteins modulate the activity of molecular chaperones. Here, we describe the S. cerevisiae TPR protein Sgt2 as interaction partner of Ssa1 and Hsp104 and as a component of the GET pathway by interacting with Get5. The GET pathway mediates the sorting of tail-anchored (TA) proteins, harboring a C-terminal trans-membrane segment, to the ER membrane. S. cerevisiae sgt2Δ cells show partial defects in TA protein sorting. Sgt2 activity in vivo relies on its N- and C-terminal domains, whereas the central TPR domain and thus chaperone interactions are dispensable. We show that TA protein sorting defects are more severe in sgt2Δ get5Δ mutants compared to single knockouts. Furthermore, overproduction of Sgt2 becomes toxic to get3Δ but not to ge... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4919772 Sat, 11 Jun 2011 01:28:32 +0100 4919772 http://www.medworm.com/index.php?rid=4919771&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.071 We report further that all three ribozymes feature a three-way helical junction outside the catalytic core in stem A, with Watson-Crick complementarity to loop nucleotides in stem B. Kinetic analyses of cleavage and ligation reactions of several variants of the sTRsV and sCYMoV hairpin ribozymes in vitro show that the presence of this junction interferes with their reactions, particularly the ligation. We provide evidence that this is not due to a presumed interaction of the afore-mentioned elements in stems A and B. The evolutionary survival of this cis-inhibiting element seems rather to be caused by the coincidence of its position with that of the hammerhead ribozyme in the other RNA polarity. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4919771 Tue, 31 May 2011 23:00:00 +0100 4919771 http://www.medworm.com/index.php?rid=4852145&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.059 Biological Chemistry 392 (6): 587-591 Abstract The 3C proteinase, essential for human poliovirus (PV) replication, has unique characteristics as its three-dimensional structure resembles chymotrypsin, but its catalytic nucleophile is a cysteine SH group rather than the OH group of serine. Here, we describe the use of tellurium compounds as inhibitors of PV3C proteinase. A rapid, stoichiometric and covalent inactivation of PV3C was observed with both a chloro-telluroxetane and a bis-vinylic organotellurane. These compounds also inhibit human cathepsins B, L, S, and K with second order rate constants higher than those obtained for PV3C. Chloro-telluroxetane inhibits replication of PV in human embryonic rhabdomyosarcoma cells in the low micromolar range and below the toxic level for the host ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4852145 Mon, 23 May 2011 15:25:18 +0100 4852145 http://www.medworm.com/index.php?rid=4852144&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.060 Biological Chemistry 392 (6): 571-585 Abstract Cathepsin E (CatE) is predominantly expressed in the rapidly regenerating gastric mucosal cells and epidermal keratinocytes, in addition to the immune system cells. However, the role of CatE in these cells remains unclear. Here we report a crucial role of CatE in keratinocyte terminal differentiation. CatE deficiency in mice induces abnormal keratinocyte differentiation in the epidermis and hair follicle, characterized by the significant expansion of corium and the reduction of subcutaneous tissue and hair follicle. In a model of skin papillomas formed in three different genotypes of syngeneic mice, CatE deficiency results in significantly reduced expression and altered localization of the keratinocyte differentiation induced proteins, keratin... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4852144 Mon, 23 May 2011 15:25:18 +0100 4852144 http://www.medworm.com/index.php?rid=4852143&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.054 Biological Chemistry 392 (6): 555-569 Abstract β-site APP-cleaving enzyme (BACE1) cleaves the wild type (WT) β-site very slowly (kcat/Km: 46.6 m-1 s-1). Therefore we searched for additional β-secretases and identified three cathepsins that split the WT β-site much faster. Human cathepsin S cleaves the WT β-site (kcat/Km: 54 700 m-1 s-1) 1170-fold faster than BACE1 and cathepsins B and L are 440- and 74-fold faster than BACE1, respectively. These cathepsins split two bonds flanking the WT β-site (K-MD-A), where the K-M bond (85%) is cleaved more efficiently than the D-A bond (15%). Cleavage at the major K-M bond yields Aβ (amyloid β-peptide) extended by N-terminal Met that should be removed to generate Aβ initiated by Asp1. The activity of cytosol and microsomal aminopeptidases ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4852143 Mon, 23 May 2011 15:25:18 +0100 4852143 http://www.medworm.com/index.php?rid=4852142&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.057 Biological Chemistry 392 (6): 547-553 Abstract Proteases are essential either for the release of neuropeptides from active or inactive proteins or for their inactivation. Neuropeptides have a fundamental role in sleep-wake cycle regulation and their actions are also likely to be regulated by proteolytic processing. Using fluorescence resonance energy transfer substrates, specific protease inhibitors and real-time PCR we demonstrate changes in angiotensin I-converting enzyme (ACE) expression and proteolytic activity in the central nervous system in an animal model of paradoxical sleep deprivation during 96 h (PSD). Male rats were distributed into five groups (PSD, 24 h, 48 h and 96 h of sleep recovery after PSD and control). ACE activity and mRNA levels were measured in hypothalamus, hi... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4852142 Mon, 23 May 2011 15:25:18 +0100 4852142 http://www.medworm.com/index.php?rid=4852141&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.050 Biological Chemistry 392 (6): 539-546 Abstract Physiological secretion of bile acids has previously been linked to the regulation of blood glucose. GLP-1 is an intestinal peptide hormone with important glucose-lowering actions, such as stimulation of insulin secretion and inhibition of glucagon secretion. In this investigation, we assessed the ability of several bile acid compounds to secrete GLP-1 in vitro in STC-1 cells. Bile acids stimulated GLP-1 secretion from 3.3- to 6.2-fold but some were associated with cytolytic effects. Glycocholic and taurocholic acids were selected for in vivo studies in normal and GLP-1R-/- mice. Oral glucose tolerance tests revealed that glycocholic acid did not affect glucose excursions. However, taurocholic acid reduced glucose excursions by 40% in normal m... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4852141 Mon, 23 May 2011 15:25:18 +0100 4852141 http://www.medworm.com/index.php?rid=4852140&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.052 Biological Chemistry 392 (6): 529-537 Abstract Oxidative stress has been linked to the podocytopathy, mes-angial expansion and progression of diabetic nephropathy. The major cell defence mechanism against oxidative stress is reduced glutathione (GSH). Some ABC transporters have been shown to extrude GSH, oxidised glutathione or their conjugates out of the cell, thus implying a role for these transporters in GSH homeostasis. We found a remarkable expression of mRNA for multidrug resistance-associated proteins (MRP/ABCC) 1, 3, 4 and 5 in rat glomeruli. Three weeks after induction of diabetes in glomeruli of streptozotocin-treated rats, we observed a decline in reduced GSH levels and an increase in the expression and activity of MRP1 (ABCC1). These lower GSH levels were improved by ex vivo tr... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4852140 Mon, 23 May 2011 15:25:18 +0100 4852140 http://www.medworm.com/index.php?rid=4852139&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.058 In this study, the dpm2 and dpm3 genes coding for the DPMII and DPMIII subunits of T. reesei DPM synthase were cloned and functionally analyzed after expression in the Saccharomyces cerevisiae dpm1Δ [genotype (BY4743; his3Δ1; /leu2Δ0; lys2Δ0; /ura3Δ0; YPR183w::kanMX4] mutant. It was found that apart from the catalytic subunit DPMI, the DPMIII subunit is also essential to form an active DPM synthase in yeast. Additional expression of the DPMII protein, considered to be a regulatory subunit of DPM synthase, decreased the enzymatic activity. We also characterized S. cerevisiae strains expressing the dpm1, 2, 3 or dpm1, 3 genes and analyzed the consequences of dpm expression on protein O-glycosylation in vivo and on the cell wall composition. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4852139 Mon, 23 May 2011 15:25:18 +0100 4852139 http://www.medworm.com/index.php?rid=4852138&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.061 This study expands our knowledge of the mechanism of action of GAPs and of the ways bacteria mimic host activities and promote catalysis of eukaryotic signaling proteins. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4852138 Mon, 23 May 2011 15:25:18 +0100 4852138 http://www.medworm.com/index.php?rid=4852137&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.056 Biological Chemistry 392 (6): 501-504 Abstract Type V collagen is known to be over-deposited in the stroma of ductal infiltrating carcinomas of the breast. When used as a substrate, type V collagen restrains growth and invasion, and affects gene expression of 8701-BC ductal infiltrating carcinomas cells. Here we supplement existing data by demonstrating type V collagen dependent upregulation of capn2 gene expression in 8701-BC cells through differential display-PCR and Western blot assays. Furthermore, we suggest that our data obtained by centrifugal sedimentation and electrophoresis strongly suggest a correlation between calpain overproduction and DNA fragmentation, since the incubation with calpain inhibitor partly reverts the latter. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4852137 Mon, 23 May 2011 15:25:18 +0100 4852137 http://www.medworm.com/index.php?rid=4852136&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.055 In this study, we investigated a tertiary association between a GAAA hairpin tetraloop in a small branching ribozyme (DiGIR1) and a receptor motif (HEG P1 motif) present in a hairpin structure on a separate mRNA molecule. DiGIR1 generates a 2′, 5′ lariat cap at the 5′ end of its downstream homing endonuclease mRNA by catalysing a self-cleavage branching reaction at an internal processing site. Upon release, the 5′ end of the mRNA forms a distinct hairpin structure termed HEG P1. Our biochemical data, in concert with molecular 3D modelling, provide experimental support for an intermolecular tetraloop receptor interaction between the L9 GAAA in DiGIR1 and a GNRA tetraloop receptor-like motif (UCUAAG-CAAGA) found within the HEG P1. The biological role of this interaction appears to be... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4852136 Mon, 23 May 2011 15:25:18 +0100 4852136 http://www.medworm.com/index.php?rid=4852135&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.069 Biological Chemistry 392 (6): I-I No abstract available (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4852135 Sat, 30 Apr 2011 23:00:00 +0100 4852135 http://www.medworm.com/index.php?rid=4696030&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.044 Biological Chemistry 392 (5): 483-489 Abstract Bacterial proteases are considered virulence factors and it is presumed that by abrogating their activity, host endogenous protease inhibitors play a role in host defense against invading pathogens. Here we present data showing that Staphylococcus aureus cysteine proteases (staphopains) are efficiently inhibited by Squamous Cell Carcinoma Antigen 1 (SCCA1), an epithelial-derived serpin. The high association rate constant (kass) for inhibitory complex formation (1.9×104 m/s and 5.8×104 m/s for staphopain A and staphopain B interaction with SCCA1, respectively), strongly suggests that SCCA1 can regulate staphopain activity in vivo at epithelial surfaces infected/colonized by S. aureus. The mechanism of staphopain inhibition by SCCA1 is appare... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4696030 Sun, 10 Apr 2011 01:31:25 +0100 4696030 http://www.medworm.com/index.php?rid=4696029&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.051 Biological Chemistry 392 (5): 475-481 Abstract Growth hormone (GH) receptor knockout (GHRKO) mice are highly insulin sensitive and long-lived. Surgical visceral fat removal (VFR) improves insulin signaling in normal mice and rats and extends longevity in rats. We have previously demonstrated decreased expression of certain pro-apoptotic genes in kidneys of GHRKO mice and suggested that this could contribute to the increased longevity of these animals. The aim of the present study was to examine the level of the following proteins: caspase-3, caspase-9, caspase-8, bax, bad, phospho-bad, bcl-2, Smac/DIABLO, Apaf-1, phospho-p53 (pp53) and cytochrome c in male GHRKO and normal (N) mice subjected to VFR or sham surgery, at approximately six months of age. The kidneys were collected two months a... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4696029 Sun, 10 Apr 2011 01:31:25 +0100 4696029 http://www.medworm.com/index.php?rid=4696028&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.053 Biological Chemistry 392 (5): 461-474 Abstract Neointimal formation in atheromatous blood vessels is associated with both growth factor-induced differentiation of smooth muscle cells and endothelial-to-mesenchymal transition. Transforming growth factor beta (TGFβ)-signaling is well known to play a critical role in the regulation of vessel remodeling as well as in atherosclerosis and restenosis. Here, we investigated the role of TGFβ1 and N-cadherin on the differentiation and migration of human vascular smooth muscle cells (VSMC). TGFβ1-treatment of cultured VSMC reduced their migratory activity as determined in cell migration assays. This reduced migration correlated with increased concentration of N-cadherin on mRNA and protein level. The TGFβ1-induced increase of N-cadherin was sensi... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4696028 Sun, 10 Apr 2011 01:31:25 +0100 4696028 http://www.medworm.com/index.php?rid=4696027&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.038 Biological Chemistry 392 (5): 449-459 Abstract Aberrant activation of STAT3 in colorectal carcinoma (CRC) tissue is correlated with elevated expression of matrix metalloproteinase-1 (MMP-1). We analyzed transcriptional regulation of the human MMP-1 promoter in CRC cells by tyrosine phosphorylated (pY-) STAT3. One of six putative STAT binding elements within a 4.3 kb MMP-1 trancriptional promoter fragment showed a particular high affinity for STAT3 in vitro. However, the most profound regulatory influence on MMP-1 promoter activity resides in a proximal region relative to the transcriptional start, bearing a pair of putative binding sites for STAT3 and AP-1. Mutational analysis of the combined STAT3/AP-1 recognition element revealed that the integrity of the STAT3 binding site is necessary... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4696027 Sun, 10 Apr 2011 01:31:25 +0100 4696027 http://www.medworm.com/index.php?rid=4696026&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.036 In this study we used a dominant-negative mutant of c-Jun, Tam67, which interferes with the functional activity of all AP-1 complexes, to investigate the requirement of AP-1 in the proliferation and cell cycle progression of cervical cancer cells. Transient and stable expression of Tam67 in CaSki cervical cancer cells resulted in decreased AP-1 activity that correlated with a significant inhibition of cell proliferation and anchorage-independent colony formation. Inhibiting AP-1 activity resulted in a two-fold increase in cells located in the G2/M phase of the cell cycle and an accompanying increase in the expression of the cell cycle regulatory protein, p21. The increase in p21 was associated with a decrease in HPV E6 expression and an increase in p53. Importantly, blocking the induction ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4696026 Sun, 10 Apr 2011 01:31:25 +0100 4696026 http://www.medworm.com/index.php?rid=4696025&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.040 Biological Chemistry 392 (5): 431-438 Abstract Plasmodium falciparum heat shock protein 70 (PfHsp70-1) is thought to play an essential role in parasite survival and virulence in the human host, making it a potential antimalarial drug target. A malate dehydrogenase based aggregation suppression assay was adapted for the screening of small molecule modulators of Hsp70. A number of small molecules of natural (marine prenylated alkaloids and terrestrial plant naphthoquinones) and related synthetic origin were screened for their effects on the protein aggregation suppression activity of purified recombinant PfHsp70-1. Five compounds (malonganenone A-C, lapachol and bromo-β-lapachona) were found to inhibit the chaperone activity of PfHsp70-1 in a concentration dependent manner, with lapachol pr... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4696025 Sun, 10 Apr 2011 01:31:25 +0100 4696025 http://www.medworm.com/index.php?rid=4696024&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.041 Biological Chemistry 392 (5): 423-429 Abstract It has been shown that apolipoprotein A-V (apoA-V) over-expression significantly lowers plasma triglyceride levels and decreases atherosclerotic lesion development. To assess the feasibility of recombinant high density lipoprotein (rHDL) reconstituted with apoA-V and apolipoprotein A-I (apoA-I) as a therapeutic agent for hyperlipidemic disorder and atherosclerosis, a series of rHDL were synthesized in vitro with various mass ratios of recombinant apoA-I and apoA-V. It is interesting to find that apoA-V of rHDL had no effect on lipoprotein lipase (LPL) activation in vitro and very low density lipoprotein (VLDL) clearance in HepG2 cells and in vivo. By contrast, LPL activation and VLDL clearance were inhibited by the addition of apoA-V to rHDL. ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4696024 Sun, 10 Apr 2011 01:31:25 +0100 4696024 http://www.medworm.com/index.php?rid=4696023&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.048 Biological Chemistry 392 (5): 415-421 Abstract The conversion of the cellular isoform of the prion protein (PrPC) into the pathologic isoform (PrPSc) is the key event in prion diseases. To study the conversion process, an in vitro system based on varying the concentration of low amounts of sodium dodecyl sulfate (SDS) has been employed. In the present study, the conversion of full-length PrPC isolated from Chinese hamster ovary cells (CHO-PrPC) was examined. CHO-PrPC harbors native, posttranslational modifications, including the GPI anchor and two N-linked glyco-sylation sites. The properties of CHO-PrPC were compared with those of full-length and N-terminally truncated recombinant PrP. As shown earlier with recombinant PrP (recPrP90-231), transition from a soluble α-helical state as know... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4696023 Sun, 10 Apr 2011 01:31:25 +0100 4696023 http://www.medworm.com/index.php?rid=4696022&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.039 Biological Chemistry 392 (5): 405-413 Abstract The expression of cathepsin L, a lysosomal protease, is known to be elevated in cancer and other pathologies. Multiple splice variants of human cathepsin L with variable 5′UTRs exist, which encode for the same protein. Previously we have observed that variant hCATL A (bearing the longest 5′UTR) was translated in vitro with significantly lower efficiency than variant hCATL AIII (bearing the shortest 5′UTR). Contrary to these findings, results of the present study reveal that in cancer cells, hCATL A mRNA exhibits higher translatability in spite of having lower stability than AIII. This is the first report demonstrating a highly contrasting trend in translation efficiencies of hCATL variants in rabbit reticulocytes and live cells. Expressi... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4696022 Sun, 10 Apr 2011 01:31:25 +0100 4696022 http://www.medworm.com/index.php?rid=4696021&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.049 Biological Chemistry 392 (5): 395-404 Abstract The products of transcription by the multisubunit enzyme RNA polymerase III (Pol III), such as 5S rRNA, tRNAs, U6 snRNA, are important for cell growth, proliferation and differentiation. The known range of the Pol III transcriptome has expanded over recent years, and novel functions of the newly discovered and already well known transcripts have been identified, including regulation of stress responses and apoptosis. Furthermore, transcription by Pol III has turned out to be strongly regulated, differing between diverse class III genes, among cell types and under stress conditions. The mechanisms involved in regulation of Pol III transcription are being elucidated and disturbances in that regulation have been implicated in various diseases, in... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4696021 Sun, 10 Apr 2011 01:31:25 +0100 4696021 http://www.medworm.com/index.php?rid=4574336&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.029 Biological Chemistry 392 (4): 387-393 Abstract Helicobacter pylori, the etiological agent of several human gastric diseases, induces the transcription factor nuclear factor-κB (NF-κB) in colonized epithelial cells leading to the release of proinflammatory mediators. Activation of NF-κB involves the IκB kinase (IKK)-complex composed of two catalytic subunits, IKKα and IKKβ, and a regulatory scaffold protein, IKKγ. IKKβ was shown to be essential for NF-κB activation in response to a variety of stimuli including H. pylori. In addition to the phosphorylation of serine residues, tyrosine phosphorylation could be crucial for IKKβ activation. Here we provide evidence that IKKβ phosphorylation is induced in lipid rafts (DRM fractions) of H. pylori-infected cells, but not TNFα-stimulate... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4574336 Sat, 12 Mar 2011 00:57:12 +0100 4574336 http://www.medworm.com/index.php?rid=4574335&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.030 Biological Chemistry 392 (4): 377-385 Abstract The low-density lipoprotein receptor (LDLR) plays a central role in cholesterol homeostasis. Here, we provide evidence that an increase in endoplasmic reticulum (ER) stress response or a disturbance of mitochondrial function inhibits LDLR expression in human liver Sk-Hep1 cells. Both organelle stresses triggered activation of activating transcription factor-3 (ATF3), which subsequently reduced LDLR expression. Serial deletion studies revealed that the LDLR promoter region within -234 bp was involved in the repression of LDLR by ATF3. In addition, we identified the region between -8 and -3 of LDLR promoter region as a putative binding site for ATF3 by using deletion construct lacking 6 bp nucleotide corresponding to this region. Transfection ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4574335 Sat, 12 Mar 2011 00:57:12 +0100 4574335 http://www.medworm.com/index.php?rid=4574334&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.033 Biological Chemistry 392 (4): 371-376 Abstract Haptoglobin (Hpt) is known to capture circulating free hemoglobin (Hb) and bind apolipoprotein (Apo) A-I or E. Here, we report that Hb can be tightly bound by most of Hpt molecules (TB-Hpt, 80%), whereas loosely bound by a minor part of them (LB-Hpt, 20%). LB-Hpt amount was significantly increased (over 60%) in patients with acute coronary syndrome. LB-Hpt bound ApoA-I and ApoE less efficiently than TB-Hpt (8- and 4-fold less, respectively) and did not affect their activity of stimulating the enzyme lecithin-cholesterol acyltransferase. LB-Hpt and TB-Hpt displayed comparable levels of nitrotyrosine residues, but differences in glycan chains. Changes in LB-Hpt level might be associated with changes in Hpt functions. (Source: Biological Chemistr... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4574334 Sat, 12 Mar 2011 00:57:12 +0100 4574334 http://www.medworm.com/index.php?rid=4574333&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.034 Biological Chemistry 392 (4): 357-369 Abstract DEAD-box proteins disrupt or remodel RNA and protein/RNA complexes at the expense of ATP. The catalytic core is composed of two flexibly connected RecA-like domains. The N-terminal domain contains most of the motifs involved in nucleotide binding and serves as a minimalistic model for helicase/nucleotide interactions. A single conserved glutamine in the so-called Q-motif has been suggested as a conformational sensor for the nucleotide state. To reprogram the Thermus thermophilus RNA helicase Hera for use of oxo-ATP instead of ATP and to investigate the sensor function of the Q-motif, we analyzed helicase activity of Hera Q28E. Crystal structures of the Hera N-terminal domain Q28E mutant (TthDEAD_Q28E) in apo- and ligand-bound forms show that Q... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4574333 Sat, 12 Mar 2011 00:57:12 +0100 4574333 http://www.medworm.com/index.php?rid=4574332&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.023 Biological Chemistry 392 (4): 347-356 Abstract Many proteins in the fibrinolysis pathway contain antiangiogenic kringle domains. Owing to the high degree of homology between kringle domains, there has been a safety concern that antiangiogenic kringles could interact with common kringle proteins during fibrinolysis leading to adverse effects in vivo. To address this issue, we investigated the effects of several antiangiogenic kringle proteins including angiostatin, apolipoprotein(a) kringles IV9-IV10-V (LK68), apolipoprotein(a) kringle V (rhLK8) and a derivative of rhLK8 mutated to produce a functional lysine-binding site (Lys-rhLK8) on the entire fibrinolytic process in vitro and analyzed the role of lysine binding. Angiostatin, LK68 and Lys-rhLK8 increased clot lysis time in a dose-depend... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4574332 Sat, 12 Mar 2011 00:57:12 +0100 4574332 http://www.medworm.com/index.php?rid=4574331&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.037 Biological Chemistry 392 (4): 337-346 Abstract Eosinophil granule proteins, eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin are members of the RNase A superfamily, which play a crucial role in host defense against various pathogens as they are endowed with several biological activities. Some of the biological activities possessed by ECP have been attributed to its strong basic character. In the current study, we have investigated the role of five unique basic residues, Arg22, Arg34, Arg61, Arg77 and His64 of ECP in its catalytic, cytotoxic, antibacterial and antiparasitic activities. These residues were changed to alanine to generate single and double mutants. None of the selected residues was found to be involved in the RNase activity of ECP. The substitution of all fi... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4574331 Sat, 12 Mar 2011 00:57:12 +0100 4574331 http://www.medworm.com/index.php?rid=4574330&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.023 Biological Chemistry 392 (4): 327-336 Abstract Supplementary to the efficient inhibition of trypsin, chymotrypsin, plasma kallikrein, and plasmin already described by the EcTI inhibitor from Enterolobium contortisiliquum, it also blocks human neutrophil elastase (Kiapp=4.3 nm) and prevents phorbol ester (PMA)-stimulated activation of matrix metalloproteinase (MMP)-2 probably via interference with membrane-type 1 (MT1)-MMP. Moreover, plasminogen-induced activation of proMMP-9 and processing of active MMP-2 was also inhibited. Furthermore, the effect of EcTI on the human cancer cell lines HCT116 and HT29 (colorectal), SkBr-3 and MCF-7 (breast), K562 and THP-1 (leukemia), as well as on human primary fibroblasts and human mesenchymal stem cells (hMSCs) was studied. EcTI inhibited in a concent... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4574330 Sat, 12 Mar 2011 00:57:12 +0100 4574330 http://www.medworm.com/index.php?rid=4574329&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.045 Biological Chemistry 392 (4): 315-325 Abstract Spinocerebellar ataxia-3 (also known as Machado-Joseph disease) is an incurable neurodegenerative disorder caused by expression of a mutant variant of ataxin-3 (ATX3) protein. Inhibiting expression of ATX3 would provide a therapeutic strategy, but indiscriminant inhibition of both wild-type and mutant ATX3 might lead to undesirable side effects. An ideal silencing agent would block expression of mutant ATX3 while leaving expression of wild-type ATX3 intact. We have previously observed that peptide nucleic acid (PNA) conjugates targeting the expanded CAG repeat within ATX3 mRNA block expression of both alleles. We have now identified additional PNAs capable of inhibiting ATX3 expression that vary in length and in the nature of the conjugated ca... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4574329 Sat, 12 Mar 2011 00:57:12 +0100 4574329 http://www.medworm.com/index.php?rid=4574328&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.043 Biological Chemistry 392 (4): 305-313 Abstract Many aspects of the RNA maturation leave traces in RNA sequencing data in the form of deviations from the reference genomic DNA. This includes, in particular, genomically non-encoded nucleotides and chemical modifications. The latter leave their signatures in the form of mismatches and conspicuous patterns of sequencing reads. Modified mapping procedures focusing on particular types of deviations can help to unravel post-transcriptional modification, maturation and degradation processes. Here, we focus on small RNA sequencing data that is produced in large quantities aimed at the analysis of microRNA expression. Starting from the recovery of many well known modified sites in tRNAs, we provide evidence that modified nucleotides are a pervasive ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4574328 Sat, 12 Mar 2011 00:57:12 +0100 4574328 http://www.medworm.com/index.php?rid=4574327&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.035 Biological Chemistry 392 (4): 299-304 Abstract RNA-dependent RNA polymerases (RdRPs) synthesize double-stranded RNAs that are processed into small RNAs and mediate gene silencing. Viral RdRPs and cellular RdRPs show little structural homology to each other. Cellular RdRPs play key roles in RNA silencing by producing complementary strands for target RNAs via Dicer-dependent and -independent mechanisms. Although the existence of a functional mammalian homolog of RdRP has long been predicted, traditional approaches to identify such enzymes were unsuccessful. Recently, human telomerase reverse transcriptase, a polymerase closely related to viral RdRPs, has been shown to function as an RdRP and contributes to RNA silencing in vivo. These findings suggest that endogenous small interfering RNAs a... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4574327 Sat, 12 Mar 2011 00:57:12 +0100 4574327 http://www.medworm.com/index.php?rid=4574326&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.046 Biological Chemistry 392 (4): 291-297 Abstract Cyanobacteria are the only prokaryotes which directly convert solar energy into biomass using oxygenic photosynthesis. Therefore, these bacteria are of interest for the production of biofuels, biotechnology and are of tremendous relevance for primary carbon fixation in many ecosystems. Mechanisms controlling gene expression cannot be understood entirely without information on the numbers and functions of regulatory RNAs. In cyanobacteria, non-coding RNAs have been characterized from simple unicellular species such as Prochlorococcus up to complex species such as Anabaena. Several of these RNAs function in the control of stress responses, photosynthesis, outer cell membrane protein biosynthesis and the differentiation of cells. (Source: Biologi... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4574326 Sat, 12 Mar 2011 00:57:12 +0100 4574326 http://www.medworm.com/index.php?rid=4574325&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.042 Biological Chemistry 392 (4): 277-289 Abstract Many prokaryotes contain the recently discovered defense system against mobile genetic elements. This defense system contains a unique type of repetitive DNA stretches, termed Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs). CRISPRs consist of identical repeated DNA sequences (repeats), interspaced by highly variable sequences referred to as spacers. The spacers originate from either phages or plasmids and comprise the prokaryotes' ‘immunological memory’. CRISPR-associated (cas) genes encode conserved proteins that together with CRISPRs make-up the CRISPR/Cas system, responsible for defending the prokaryotic cell against invaders. CRISPR-mediated resistance has been proposed to involve three stages: (i) CRISPR-Adaptatio... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4574325 Sat, 12 Mar 2011 00:57:12 +0100 4574325 http://www.medworm.com/index.php?rid=4574324&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.047 Biological Chemistry 392 (4): 275-275 No abstract available (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4574324 Sat, 12 Mar 2011 00:57:12 +0100 4574324 http://www.medworm.com/index.php?rid=4436206&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.021 In this study, inactivation of human kininogens after oxidation with the myeloperoxidase-H2O2-chloride system was observed and analyzed by protein chemistry methods. The kinin release from oxidized kininogens by major kinin-producing enzymes, plasma and tissue kallikreins, proceed with a very low rate. This effect was assigned to apparent inability of kallikreins to process the kinin N-terminus owing to the conversion of the adjacent Met-361 residue to methionine sulfoxide. Additionally, the oxidized high-molecular mass kininogen lost its natural ability to bind plasma prekallikrein. This effect was assigned to the oxidation of Trp-569 residue within the prekallikrein-binding region which is subsequently destructed owing to cleavage of the peptide bond after that residue. One possible path... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4436206 Fri, 04 Feb 2011 23:28:37 +0100 4436206 http://www.medworm.com/index.php?rid=4436205&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.026 Biological Chemistry 392 (3): 249-262 Abstract 14-3-3 proteins are major regulators in plant development and physiology including primary metabolism and signal transduction pathways, typically via a phosphorylation-dependent interaction with a target protein. Four full-length 14-3-3 isoforms were identified in pollen grains of Lilium longiflorum by screening of a cDNA library and RACE (rapid amplification of cDNA ends)-PCR. Mass spectrometry analysis of partially purified 14-3-3s confirmed the presence of the four isoforms but also indicated the presence of additional, less abundant 14-3-3 isoforms in lily pollen. Separation of partially purified 14-3-3 proteins by two-dimensional gel electrophoresis resulted in nine spots that mainly contained the four major 14-3-3 isoforms. In a first st... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4436205 Fri, 04 Feb 2011 23:28:37 +0100 4436205 http://www.medworm.com/index.php?rid=4436204&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.022 Biological Chemistry 392 (3): 239-248 Abstract The Mss4 (mammalian suppressor of yeast Sec4) is an evolutionarily highly conserved protein and is expressed in all mammalian tissues. Although its precise biological function is still elusive, it has been shown to associate with a subset of secretory Rab proteins (Rab1b, Rab3a, Rab8a, Rab10) and to possess a rather low guanine nucleotide exchange factor (GEF) activity towards them in vitro (Rab1, Rab3a and Rab8a). By screening a human placenta cDNA library with Mss4 as bait, we identified several Rab GTPases (Rab12, Rab13 and Rab18) as novel Mss4-binding Rab proteins. Only exocytic but no endocytic Rab GTPases were found in our search. The binding of Mss4 to Rab proteins was confirmed by direct yeast two-hybrid interaction, by co-immunoprecip... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4436204 Fri, 04 Feb 2011 23:28:37 +0100 4436204 http://www.medworm.com/index.php?rid=4436203&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.024 Biological Chemistry 392 (3): 233-237 Abstract Cellular dipeptidyl peptidase IV (DP IV, CD26) and amino-peptidase N (APN, CD13) play regulatory roles in T cell activation and represent potential targets for treatment of inflammatory disorders. We have developed a novel therapeutic strategy, ‘peptidase-targeted Immunoregulation’ (PETIR™), which simultaneously targets both cellular DP IV and APN via selective binding sites different from the active sites with a single inhibitor. To prove the therapeutic concept of PETIR™ in autoimmunity of the central nervous system (CNS), we evaluated the effect of a single substance, PETIR-001, in an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) in SJL/J mice. Administration of PETIR-001 significantly delayed a... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4436203 Fri, 04 Feb 2011 23:28:37 +0100 4436203 http://www.medworm.com/index.php?rid=4436202&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.028 Biological Chemistry 392 (3): 223-231 Abstract Dipeptidyl peptidase 4/CD26 (DP4) is a multifunctional serine protease liberating dipeptide from the N-terminus of (oligo)peptides which can modulate the activity of these peptides. The enzyme is involved in physiological processes such as blood glucose homeostasis and immune response. DP4 substrate specificity is characterized in detail using synthetic dipeptide derivatives. The specificity constant kcat/Km strongly depends on the amino acid in P1-position for proline, alanine, glycine and serine with 5.0×105 m-1s-1, 1.8×104 m-1s-1, 3.6×102 m-1s-1, 1.1×102 m-1s-1, respectively. By contrast, kinetic investigation of larger peptide substrates yields a different pattern. The specific activity of DP4 for neuropeptide Y (NPY) cleavage comp... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4436202 Fri, 04 Feb 2011 23:28:37 +0100 4436202 http://www.medworm.com/index.php?rid=4436201&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.003 Biological Chemistry 392 (3): 217-221 Abstract Substance P (SP), an undecapeptide belonging to the tachykinin family, is released during the activation of sensory nerves, and causes vasodilation, edema and pain through activation of tissular Neurokinin 1 receptors. SP proinflammatory effects are terminated by angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), while the aminopeptidase dipeptidylpeptidase IV (DPPIV) can also play a role. The aim of this randomized, crossover, double-blind study was to assess the cutaneous vasoreactivity (flare and wheal reaction, burning pain sensation) to intradermal injection of ascending doses of SP in six volunteers receiving a single therapeutic dose of the DPPIV inhibitor sitagliptin or a matching placebo. Cutaneous SP challenges prod... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4436201 Fri, 04 Feb 2011 23:28:37 +0100 4436201 http://www.medworm.com/index.php?rid=4436200&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.027 Biological Chemistry 392 (3): 209-215 Abstract GIP metabolite [GIP (3–42)] and GLP-1 metabolite [GLP-1 (9–36) amide] have been reported to differ with regard to biological actions. Systemic DPP-4 inhibition can therefore reveal different actions of GIP and GLP-1. In catheter wearing Wistar rats, insulinotropic effects of equipotent doses of GIP (2.0 nmol/kg) and GLP-1 (7–36) amide (4.0 nmol/kg) and vehicle were tested in the absence/presence of DPP-4 inhibition. Blood glucose and insulin were frequently sampled. DPP-4 inhibitor was given at -20 min, the incretin at -5 min and the intravenous glucose tolerance test (0.4 g glucose/kg) commenced at 0 min. G-AUC and I-AUC, insulinogenic index and glucose efflux, were calculated from glucose and insulin curves. Systemic DPP-4 inhibi... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4436200 Fri, 04 Feb 2011 23:28:37 +0100 4436200 http://www.medworm.com/index.php?rid=4436199&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.119 Biological Chemistry 392 (3): 199-207 Abstract Seprase or fibroblast activation protein-α (FAP-α) is a cell-surface serine protease that was previously described nearly exclusively on reactive and tumor stromal fibroblasts and thought to be involved in tissue remodeling. We investigated the expression and significance of FAP-α in astrocytomas/glioblastomas. As shown by quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohisto-chemistry, FAP-α was elevated in whole glioblastoma tissues and in particular in most glioma cells in situ and in vitro. In glioma stem-like cells (gliospheres), FAP-α was detected at low levels; however, FAP-α was considerably induced upon differentiation with 10% fetal calf serum. To explore its functional role, FAP-α was silenced ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4436199 Fri, 04 Feb 2011 23:28:37 +0100 4436199 http://www.medworm.com/index.php?rid=4436198&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.002 In conclusion, our results support a highly regulated expression of individual DPPs in ECs, with a spatial heterogeneity in the cardiovascular tree. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4436198 Fri, 04 Feb 2011 23:28:37 +0100 4436198 http://www.medworm.com/index.php?rid=4436197&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.025 Biological Chemistry 392 (3): 169-187 Abstract The discovery of the DP4-related enzymes DP8 and DP9 raised controversial discussion regarding the physiological and pathophysiological function of distinct members of the DP4 family. Particularly with regard to their potential relevance in regulating immune functions, it is of interest to know which role the subcellular distribution of the enzymes play. Synthetic substrates as well as low molecular weight inhibitors are widely used as tools, but little is yet known regarding their features in cell experiments, such as their plasma membrane penetration capacity. The fluorogenic substrates Gly-Pro-AMC or (Ala-Pro)2-R110 predominantly detect plasma membrane-bound activities of viable cells (less than 0.1% of fluorochromes R110 or AMC inside viab... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4436197 Fri, 04 Feb 2011 23:28:37 +0100 4436197 http://www.medworm.com/index.php?rid=4436196&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.008 In this study, we show particularly for immune cells that DPIV and not DP8 or DP9 is the most potent member of the DPIV family in regulating cellular immune functions. Moreover, we provide evidence that soluble and cellular DPIV differ in functions and hand-ling of substrates and inhibitors owing to the different accessibility of peptide substrates to the two access paths of DPIV. The different functions are based on the favored access path of the central pore of cellular DPIV and a special central pore binding site which assists substrate access to the active site of the enzyme. The newly discovered central pore binding site mediates an autosterical regulation of cellular DPIV and is its most crucial target site to regulate cellular functions such as growth and cytokine production. Neurop... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4436196 Fri, 04 Feb 2011 23:28:37 +0100 4436196 http://www.medworm.com/index.php?rid=4436195&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.032 Biological Chemistry 392 (3): 151-152 No abstract available (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4436195 Fri, 04 Feb 2011 23:28:37 +0100 4436195 http://www.medworm.com/index.php?rid=4342177&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.004 Biological Chemistry 392 (1-2): 143-150 Abstract High-resolution microscopy techniques provide a plethora of information on biological structures from the cellular level down to the molecular level. In this review, we present the unique capabilities of transmission electron and atomic force microscopy to assess the structure, oligomeric state, function and dynamics of channel and transport proteins in their native environment, the lipid bilayer. Most importantly, membrane proteins can be visualized in the frozen-hydrated state and in buffer solution by cryo-transmission electron and atomic force microscopy, respectively. We also illustrate the potential of the scintillation proximity assay to study substrate binding of detergent-solubilized transporters prior to crystallization and structu... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4342177 Thu, 13 Jan 2011 23:38:48 +0100 4342177 http://www.medworm.com/index.php?rid=4342176&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.001 Biological Chemistry 392 (1-2): 135-142 Abstract Conformational changes of proteins can be monitored in real time by fluorescence resonance energy transfer (FRET). Two different fluorophores have to be attached to those protein domains which move during function. Distance fluctuations between the fluorophores are measured by relative fluorescence intensity changes or fluorescence lifetime changes. The rotary mechanics of the two motors of FoF1-ATP synthase have been studied in vitro by single-molecule FRET. The results are summarized and perspectives for other transport ATPases are discussed. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4342176 Thu, 13 Jan 2011 23:38:48 +0100 4342176 http://www.medworm.com/index.php?rid=4342175&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.010 Biological Chemistry 392 (1-2): 125-134 Abstract Two families of proteins, the bestrophins (Best) and the recently cloned TMEM16 proteins (anoctamin, Ano), recapitulate properties of Ca2+-activated Cl- currents. Best1 is strongly expressed in the retinal pigment epithelium and could have a function as a Ca2+-activated Cl- channel as well as a regulator of Ca2+ signaling. It is also present at much lower levels in other cell types including epithelial cells, where it regulates plasma membrane localized Cl- channels by controlling intracellular Ca2+ levels. Best1 interacts with important Ca2+-signaling proteins such as STIM1 and can interact directly with other Ca2+-activated Cl- channels such as TMEM16A. Best1 is detected in the endoplasmic reticulum (ER) where it shapes the dynamic ER stru... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4342175 Thu, 13 Jan 2011 23:38:48 +0100 4342175 http://www.medworm.com/index.php?rid=4342174&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.014 Biological Chemistry 392 (1-2): 117-124 Abstract The response to chemotherapy by tumor cells depends on the concentration of cytostatics accumulated inside the cells. The accumulation of anticancer drugs in tumor cells is mainly dependent on functional expression of efflux and influx transporters and to a minor extent on passive diffusion through the membrane. Efflux transporters of the ABC family are partially responsible for the chemoresistance of cancer cells by secreting these cytostatics. Over the past decades, the role of ABC transporters in the chemoresistance of various malignant tumors has been very well documented. By contrast, very little is known about the impact on tumor therapy of influx transporters belonging to the solute carrier transporters (SLC family). In this review, w... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4342174 Thu, 13 Jan 2011 23:38:48 +0100 4342174 http://www.medworm.com/index.php?rid=4342173&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.016 Biological Chemistry 392 (1-2): 103-115 Abstract Amphetamine (‘Speed’), methamphetamine (‘Ice’) and its congener 3,4-methylenedioxymethamphetamine (MDMA; ‘Ecstasy’) are illicit drugs abused worldwide for their euphoric and stimulant effects. Despite compelling evidence for chronic MDMA neurotoxicity in animal models, the physiological consequences of such toxicity in humans remain unclear. In addition, distinct differences in the metabolism and pharmacokinetics of MDMA between species and different strains of animals prevent the rationalisation of realistic human dose paradigms in animal studies. Here, we attempt to review amphetamine toxicity and in particular MDMA toxicity in the pathogenesis of exemplary human pathologies, independently of confounding environmental factors s... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4342173 Thu, 13 Jan 2011 23:38:48 +0100 4342173 http://www.medworm.com/index.php?rid=4342172&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.009 Biological Chemistry 392 (1-2): 95-101 Abstract Organic cation transporters (OCTs) of the SLC22 family play a pivotal role in distribution and excretion of cationic drugs. They mediate electrogenic translocation of cations in both directions. OCTs are polyspecific transporters. During substrate translocation they perform a series of conformational changes involving an outward-facing conformation, an occluded state and an inward-facing conformation. Mutagenesis of OCT1 in combination with homology modeling showed that identical amino acids form the innermost parts of the outward-open and inward-open binding clefts. In addition to low affinity substrate binding sites, OCT1 contains high affinity substrate binding sites that can mediate inhibition via non-transported compounds. (Source: Biolo... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4342172 Thu, 13 Jan 2011 23:38:48 +0100 4342172 http://www.medworm.com/index.php?rid=4342171&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.017 Biological Chemistry 392 (1-2): 77-94 Abstract Membrane transporters are major determinants for the pharmacokinetic, safety and efficacy behavior of drugs. Available technologies to study function and structure of transport proteins has strongly stimulated research in transporter biology and uncovered their importance for the drug discovery and development process, especially for drug absorption and disposition. Physiological transport systems are investigated as potential ferries to improve drug absorption and membrane permeation and to achieve organ-specific drug action. In particular, the bile acid transport systems in the liver and the small intestine and the oligopeptide transporters are of significant importance for molecular drug delivery. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4342171 Thu, 13 Jan 2011 23:38:48 +0100 4342171 http://www.medworm.com/index.php?rid=4342170&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.015 Biological Chemistry 392 (1-2): 67-76 Abstract While accumulating evidence indicates that P4-ATPases catalyze phospholipid transport across cellular bilayers, their kinship to cation-pumping ATPases has raised fundamental questions concerning the underlying flippase mechanism. Loss of P4-ATPase function perturbs vesicle formation in late secretory and endocytic compartments. An intriguing concept is that P4-ATPases help drive vesicle budding by generating imbalances in transbilayer lipid numbers. Moreover, activation of P4-ATPases by phosphoinositides and other effectors of coat recruitment provide a potential mechanism to confine flippase activity to sites of vesicle biogenesis. These developments have raised considerable interest in understanding the mechanism, regulation and biological ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4342170 Thu, 13 Jan 2011 23:38:48 +0100 4342170 http://www.medworm.com/index.php?rid=4342169&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.007 Biological Chemistry 392 (1-2): 61-66 Abstract The transporter associated with antigen processing-like (TAPL) is a polypeptide transporter translocating cytosolic peptides into the lumen of lysosomes driven by ATP hydrolysis. TAPL belongs to the family of ABC transporters and forms a homodimer. This ABC transporter not only shows a broad tissue but also a wide phylogenetic distribution, because orthologs are still found in nematodes and insects. Here, we present the topology, substrate specificity, and distribution of this intracellular polypeptide transporter. Additionally, we will discuss its proposed physiological functions such as housekeeping together with a specialized factor for metabolite storage as well as for the adaptive immunity. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4342169 Thu, 13 Jan 2011 23:38:48 +0100 4342169 http://www.medworm.com/index.php?rid=4342168&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.011 Biological Chemistry 392 (1-2): 53-60 Abstract A subset of the family of ATP-binding cassette (ABC) transporters has been in focus owing to their involvement in conferring multidrug resistance in cancer cells and among immune compromised individuals. Saccharomyces cerevisiae is protected against xenobiotics by similar machineries that are part of the pleitropic drug resistance (PDR) network. The ABC transporter Pdr5 is an important member of this PDR network in yeast and is involved in cellular detoxification by the efflux of a wide variety of drugs and substrates. In this review, we focus on the aspects of detergent effects and the degeneracy in conserved sequences that is observed in the nucleotide binding domains of Pdr5 and discuss their functional relevance. (Source: Biological Chemis... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4342168 Thu, 13 Jan 2011 23:38:48 +0100 4342168 http://www.medworm.com/index.php?rid=4342167&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.012 Biological Chemistry 392 (1-2): 39-52 Abstract In Escherichia coli the Fhu, Fep and Fec transport systems are involved in the uptake of chelated ferric iron-siderophore complexes, whereas in pathogenic strains heme can also be used as an iron source. An essential step in these pathways is the movement of the ferric-siderophore complex or heme from the outer membrane transporter across the periplasm to the cognate cytoplasmic membrane ATP-dependent transporter. This is accomplished in each case by a dedicated periplasmic binding protein (PBP). Ferric-siderophore binding PBPs belong to the PBP protein superfamily and adopt a bilobal type III structural fold in which the two independently folded amino and carboxy terminal domains are linked together by a single long α-helix of approximately ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4342167 Thu, 13 Jan 2011 23:38:48 +0100 4342167 http://www.medworm.com/index.php?rid=4342166&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.006 Biological Chemistry 392 (1-2): 29-37 Abstract The ATP-binding cassette (ABC) transporter genes represent the largest family of transporters and these genes are abundant in the genome of all vertebrates. Through analysis of the genome sequence databases we have characterized the full complement of ABC genes from several mammals and other vertebrates. Multiple gene duplication and deletion events were identified in ABC genes in different lineages indicating that the process of gene evolution is still ongoing. Gene duplication resulting in either gene birth or gene death plays a major role in the evolution of the vertebrate ABC genes. The understanding of this mechanism is important in the context of human health because these ABC genes are associated with human disease, involving nearly all... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4342166 Thu, 13 Jan 2011 23:38:48 +0100 4342166 http://www.medworm.com/index.php?rid=4342165&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.005 Biological Chemistry 392 (1-2): 21-27 Abstract Omp85-like proteins are evolutionary ancient components of bacterial outer membranes and their evolutionary offspring. As a consequence, proteins of this family can be found in the outer membrane systems of Gram-negative bacteria and endosymbiotically derived organelles. In the different membranes, they perform distinct functions such as catalyzing protein insertion into or protein transport across the bilayer. Here, the knowledge on the Omp85-like proteins in the eukaryotic system with regard to structural properties and physiological behavior is summarized. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4342165 Thu, 13 Jan 2011 23:38:48 +0100 4342165 http://www.medworm.com/index.php?rid=4342164&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.013 Biological Chemistry 392 (1-2): 13-19 Abstract Members of the YidC/Oxa1/Alb3 protein family facilitate the insertion, folding and assembly of proteins of the inner membranes of bacteria and mitochondria and the thylakoid membrane of plastids. All homologs share a conserved hydrophobic core region comprising five transmembrane domains. On the basis of phylogenetic analyses, six subgroups of the family can be distinguished which presumably arose from three independent gene duplications followed by functional specialization. During evolution of bacteria, mitochondria and chloroplasts, subgroup-specific regions were added to the core domain to facilitate the association with ribosomes or other components contributing to the substrate spectrum of YidC/Oxa1/Alb3 proteins. (Source: Biological Che... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4342164 Thu, 13 Jan 2011 23:38:48 +0100 4342164 http://www.medworm.com/index.php?rid=4342163&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.018 Biological Chemistry 392 (1-2): 5-12 Abstract We herein report recent advances in our understanding of transport protein evolution. Numerous families of complex transmembrane transport proteins are believed to have arisen from short channel-forming amphipathic or hydrophobic peptides by various types of intragenic duplication events. Distinct pathways distinguish families, demonstrating independent origins for some, and allowing assignment of others to superfamilies. Some families have diversified in topology, whereas others have remained uniform. An example of ‘retroevolution’ was discovered where a more complex carrier gave rise to a structurally and functionally simpler channel. The results described in this review article expand our understanding of protein evolution. (Source: Biol... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4342163 Thu, 13 Jan 2011 23:38:48 +0100 4342163 http://www.medworm.com/index.php?rid=4342162&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.019 Biological Chemistry 392 (1-2): 3-3 No abstract available (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4342162 Thu, 13 Jan 2011 23:38:48 +0100 4342162 http://www.medworm.com/index.php?rid=4342161&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2011.020 Biological Chemistry 392 (1-2): 1-1 No abstract available (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4342161 Sat, 01 Jan 2011 00:00:00 +0100 4342161 http://www.medworm.com/index.php?rid=4189102&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.150 Biological Chemistry 391 (12): 1475-1476 No abstract available (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4189102 Tue, 23 Nov 2010 02:10:39 +0100 4189102 http://www.medworm.com/index.php?rid=4189101&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.140 Biological Chemistry 391 (12): 1469-1473 Abstract Renin is the first enzyme in the renin-angiotensin-aldosterone system which is the principal regulator of blood pressure and hydroelectrolyte balance. Previous studies suggest that cathepsin B is the activator of the prorenin zymogen. Here, we show no difference in plasma renin activity, or mean arterial blood pressure between wild-type and cathepsin B knockout mice. To account for potential gene compensation, a potent, selective, reversible cathepsin B inhibitor was developed to determine the role of cathepsin B on prorenin processing in rats. Pharmacological inhibition of cathepsin B in spontaneously hypertensive and double transgenic rats did not result in a reduction in renal mature renin protein levels or plasma renin activity. We conc... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4189101 Tue, 23 Nov 2010 02:10:39 +0100 4189101 http://www.medworm.com/index.php?rid=4189100&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.139 Biological Chemistry 391 (12): 1451-1459 Abstract Functional effects of acute and prolonged (48 h) exposure to the biguanide drug metformin were examined in the clonal pancreatic β-cell line, BRIN-BD11. Effects of metformin on prolonged exposure to excessive increased concentrations of glucose and palmitic acid were also assessed. In acute 20-min incubations, 12.5–50 μm metformin did not alter basal (1.1 mm glucose) or glucose-stimulated (16.7 mm glucose) insulin secretion. However, higher concentrations of metformin (100–1000 μm) increased (1.3–1.5-fold; p (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4189100 Tue, 23 Nov 2010 02:10:39 +0100 4189100 http://www.medworm.com/index.php?rid=4189099&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.141 In this study we show: (i) bile acid retention in ob/ob mice, (ii) a resulting FXR upregulation and binding to the IR-1 element in ob/ob animals and (iii) concomitant activation of the fatty acid synthase as a potential lipogenic FXR target gene in vivo. The present study suggests a potential role of hepatic bile acid retention and FXR activation in the induction of lipogenic target genes. Differences between intestinal and hepatic FXR could explain apparent contradictory information regarding its effects on fatty liver disease. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4189099 Tue, 23 Nov 2010 02:10:39 +0100 4189099 http://www.medworm.com/index.php?rid=4189098&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.130 Biological Chemistry 391 (12): 1419-1428 Abstract Although enzymes responsible for the cyclization of amino-terminal glutamine residues are present in both plant and mammal species, none have yet been characterized in bacteria. Based on low sequence homologies to plant glutaminyl cyclases (QCs), we cloned the coding sequences of putative microbial QCs from Zymomonas mobilis (ZmQC) and Myxococcus xanthus (MxQC). The two recombinant enzymes exhibited distinct QC activity, with specificity constants kcat/Km of 1.47±0.33 mm-1 s-1 (ZmQC) and 142±32.7 mm-1 s-1 (MxQC) towards the fluorescent substrate glutamine-7-amino-4-methyl-coumarine. The measured pH-rate profile of the second order rate constant displayed an interesting deviation towards the acidic limb of the pH chart in the case of ZmQ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4189098 Tue, 23 Nov 2010 02:10:39 +0100 4189098 http://www.medworm.com/index.php?rid=4189097&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.138 Biological Chemistry 391 (12): 1411-1417 Abstract The initial step in twin arginine translocation (Tat)-dependent thylakoid transport of the 16/23 chimera is the interaction of the protein with the lipid bilayer. It results in the formation of the early translocation intermediate Ti-1, which is represented by a protease-protected fragment of 14 kDa. Cys-scanning mutagenesis in combination with in thylakoido and liposome insertion assays was used to precisely map this membrane-interacting and protease-protected fragment within the 16/23 chimera. The fragment comprises 124 residues, which are provided both by the transit peptide (31 residues) and the mature protein (93 residues), demonstrating that the passenger protein directly participates in membrane binding. The implications of this fin... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4189097 Tue, 23 Nov 2010 02:10:39 +0100 4189097 http://www.medworm.com/index.php?rid=4182359&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.129 Biological Chemistry 391 (11): 1341-1363 Abstract The evolutionarily ancient low-density lipoprotein (LDL) receptor gene family represents a class of widely expressed cell surface receptors. Since the dawn of the first primitive multicellular organisms, several structurally and functionally distinct families of lipoprotein receptors have evolved. In accordance with the now obsolete ‘one-gene-one-function’ hypothesis, these cell surface receptors were orginally perceived as mere transporters of lipoproteins, lipids, and nutrients or as scavenger receptors, which remove other kinds of macromolecules, such as proteases and protease inhibitors from the extracellular environment and the cell surface. This picture has since undergone a fundamental change. Experimental evidence has replaced t... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4182359 Fri, 19 Nov 2010 16:55:14 +0100 4182359 http://www.medworm.com/index.php?rid=4182358&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.133 Biological Chemistry 391 (11): 1333-1339 Abstract The aim of this study was to investigate whether fine and ultrafine carbon black (fC and ufC), and fine and ultrafine silica (fS, ufS) particles affect gap junctional intercellular communication (GJIC) in rat lung epithelial cells. Exposure of cells to subcytotoxic doses of ufC, fS and ufS resulted in a 63%, 59% and 77% reduction of GJIC, respectively, as determined in a dye transfer assay. In contrast to ufC, fC did not significantly alter GJIC. Changes in subcellular localization of the major gap junction protein in RLE cells, connexin-43 (Cx43), and of β-catenin were observed in cells exposed to ufC, fS or ufS. The loss of GJIC was counteracted by N-acetyl cysteine and was largely prevented by specific inhibitors of epidermal growth fac... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4182358 Fri, 19 Nov 2010 16:55:14 +0100 4182358 http://www.medworm.com/index.php?rid=4182357&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.131 Biological Chemistry 391 (11): 1327-1332 Abstract Owing to their specific physico/chemical properties, engineered as well as environmental nanoparticles can induce pathogenic endpoints in humans. Earlier studies demonstrated that pure carbon nanoparticles induce cell signaling events at the level of membrane receptor activation in lung epithelial cells. As a possible link between receptor activation and subsequent MAP-kinase signaling, the involvement of Src family kinases was investigated in cell lines of organs potentially exposed to environmental nanoparticles. Human cells from bronchus, intestine, and skin (keratinocytes) as well as rat lung epithelial cells showed similar time patterns for the activation of mitogen-activated protein kinases Erk1/2 as well as Src family kinases (SFK) w... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4182357 Fri, 19 Nov 2010 16:55:14 +0100 4182357 http://www.medworm.com/index.php?rid=4182356&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.132 Biological Chemistry 391 (11): 1315-1325 Abstract Macrophages are tightly associated with inflammatory diseases as well as carcinogenesis, and therefore represent promising targets for drug delivery and gene transfer. We have recently established a novel protein delivery system based on the binary C2 toxin of Clostridium botulinum and streptavidin, allowing the uptake of exogenous biotinylated molecules into mammalian cells. Here, we applied this C2-streptavidin delivery system to macrophages and other leukocytes. First, the effect of wild-type C2 toxin on different leukocyte cell lines was tested, indicating no differences in sensitivity. Next, the uptake and stability of the engineered C2-streptavidin was analyzed in macrophages and Jurkat T-cells, showing internalization into the cytoso... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4182356 Fri, 19 Nov 2010 16:55:14 +0100 4182356 http://www.medworm.com/index.php?rid=4182355&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.115 Biological Chemistry 391 (11): 1305-1313 Abstract Cytochrome P450 (CYP) hemoproteins play an important role in hepatic biotransformation. Recently, β-catenin and Ha-ras signaling have been identified as players controlling transcription of various CYP genes in mouse liver. The aim of the present study was to analyze the role of β-catenin and Ha-ras in the regulation of heme synthesis. Heme synthesis-related gene expression was analyzed in normal liver, in transgenic mice expressing activated β-catenin or Ha-ras, and in hepatomas. Regulation of the aminolevulinate dehydratase promoter was studied in vitro. Elevated expression of mRNAs and proteins involved in heme biosynthesis was linked to β-catenin activation in perivenous hepatocytes, in transgenic hepatocytes, and in hepatocellular ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4182355 Fri, 19 Nov 2010 16:55:14 +0100 4182355 http://www.medworm.com/index.php?rid=4182354&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.135 In conclusion, cadmium can augment monocytic differentiation by activating ERK1/2 signaling, leading to increased generation of functional monocytes. These increased monocyte numbers could contribute to the impact of cadmium on the immune system owing to their role in the production of pro-inflammatory cytokines and activation of T-cells by antigen presentation. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4182354 Fri, 19 Nov 2010 16:55:14 +0100 4182354 http://www.medworm.com/index.php?rid=4182353&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.134 Biological Chemistry 391 (11): 1281-1293 Abstract Glucosinolates (GLSs) present in Brassica vegetables serve as precursors for biologically active metabolites, which are released by myrosinase and induce phase 2 enzymes via the activation of Nrf2. Thus, GLSs are generally considered beneficial. The pattern of GLSs in plants is various, and contents of individual GLSs change with growth phase and culture conditions. Whereas some GLSs, for example, glucoraphanin (GRA), the precursor of sulforaphane (SFN), are intensively studied, functions of others such as the indole GLS neoglucobrassicin (nGBS) are rather unknown as are functions of combinations thereof. We therefore investigated myrosinase-treated GRA, nGBS and synthetic SFN for their ability to induce NAD(P)H:quinone oxidoreductase 1 (NQ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4182353 Fri, 19 Nov 2010 16:55:14 +0100 4182353 http://www.medworm.com/index.php?rid=4182352&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.136 Biological Chemistry 391 (11): 1265-1279 Abstract The formation of reactive oxygen species (ROS) can be induced by xenobiotic substances, such as redox cycling molecules, but also by endogenous substances such as hormones and cytokines. Recent research shows the importance of ROS in cellular signaling. Here, the signaling pathways of the two blood pressure-regulating hormones angiotensin II and aldosterone are presented, focusing on both their physiological effects and the change of signaling owing to the action of increased concentrations or prolonged exposure. When present in high concentrations, both angiotensin II and aldosterone, as various other endogenous substances, activate NADPH oxidase, which produces superoxide. In this review the generation of superoxide anions and hydrogen pe... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4182352 Fri, 19 Nov 2010 16:55:14 +0100 4182352 http://www.medworm.com/index.php?rid=4182351&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.137 Biological Chemistry 391 (11): 1249-1264 Abstract Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality worldwide. For example, the Veterans Administration Cooperative Studies reported that patients with cirrhosis and superimposed alcoholic hepatitis had a 4-year mortality of >60%. The poor prognosis of ALD implies that preventing disease progression would be more effective than treating end-stage liver disease. An obvious avenue of prevention would be to remove the damaging agent; however, the infamously high rate of recidivism in alcoholics makes maintaining abstinence a difficult treatment goal to prevent ALD. Indeed, although the progression of ALD is well-characterized, there is no universally accepted therapy available to halt or reverse this process in human... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4182351 Fri, 19 Nov 2010 16:55:14 +0100 4182351 http://www.medworm.com/index.php?rid=4182350&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.128 Biological Chemistry 391 (11): 1235-1248 Abstract Depending on their chemical structure and properties, environmental chemicals and other xenobiotics that enter the cell can affect cellular function by either nonselective binding to cellular macromolecules or by interference with cellular receptors, which would initiate a more defined cell biological response. One of these intracellular chemosensor molecules is the aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family that is known to mediate the biochemical and toxic effects of dioxins, polyaromatic hydrocarbons and related compounds. Numerous investigations have revealed that the AhR is not only a master regulator of drug metabolism activated by anthropogenic chemicals, but is also triggered by natural and endoge... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4182350 Fri, 19 Nov 2010 16:55:14 +0100 4182350 http://www.medworm.com/index.php?rid=4178437&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.145 In this study, the increase of SARS-CoV 3CLpro peptidase activity in presence of kosmotropic salts and crowding agents is described. The activation followed the Hofmeister series of anions, with two orders of magnitude enhancement in the presence of Na2SO4, whereas the crowding agents polyethylene glycol and bovine serum albumin increased the hydrolytic rate up to 3 times. Kinetic determinations of the monomer dimer dissociation constant (Kd) indicated that activation was a result of a more active dimer, without significant changes in Kd values. The activation was found to be independent of substrate length and was derived from both kcat increase and Km decrease. The viral peptidase activation described here could be related to the crowded intracellular environment and indicates a further... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4178437 Thu, 18 Nov 2010 17:09:56 +0100 4178437 http://www.medworm.com/index.php?rid=4178436&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.146 Biological Chemistry 391 (12): 1429-1439 Abstract Haptoglobin is an acute phase glycoprotein, secreted by hepatocytes and other types of cells including keratinocytes. Haptoglobin has been suggested to impair the immune response, inhibit gelatinases in the extracellular matrix and promote angiogenesis, but its role in psoriasis is obscure to date. Changes in haptoglobin glycan structure were observed in several diseases. The aim of this study was to investigate whether haptoglobin displays glycan variations in psoriasis. We found that the pattern of plasma haptoglobin glycoforms, following two-dimensional electrophoresis, exhibited significant quantitative differences in spot intensities between patients and controls. Quantitative and qualitative differences in glycan mass, between patient... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4178436 Thu, 18 Nov 2010 17:09:56 +0100 4178436 http://www.medworm.com/index.php?rid=4178435&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.147 Biological Chemistry 391 (12): 1401-1410 Abstract Hepatoma-derived growth factor (HDGF) was first purified as a growth factor secreted by hepatoma cells. It promotes angiogenesis and has been related to tumorigenesis. To date, little is known about the molecular mechanisms of HDGF functions and especially its routes or regulation of secretion. Here we show that secretion of HDGF requires the N-terminal 10 amino acids and that this peptide can mediate secretion of other proteins, such as enhanced green fluorescent protein, if fused to their N-terminus. Our results further demonstrate that cysteine residues at positions 12 and 108 are linked via an intramolecular disulfide bridge. Surprisingly, phosphorylation of serine 165 in the C-terminal part of HDGF plays a critical role in the secretio... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4178435 Thu, 18 Nov 2010 17:09:56 +0100 4178435 http://www.medworm.com/index.php?rid=4178434&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.143 Biological Chemistry 391 (12): 1391-1400 Abstract αB-Crystallin plays an important part in cataract development. A novel mutation (R11H) was previously detected by our group. In the present study, we set out to investigate the possible molecular mechanism by which the R11H mutation causes cataract. We found that the mutant αB-crystallin exhibits folding defects, decreased surface hydrophobicity and enhanced chaperone-like activity compared with the wild-type αB-crystallin. The mutant protein shows nearly the same molecular mass and thermal stability as the wild-type form. Transfection studies revealed that the R11H mutant was remarkably similar to the wild-type protein in its subcellular distribution, but has an abnormal ability to induce cell apoptosis. These results suggest that the c... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4178434 Thu, 18 Nov 2010 17:09:56 +0100 4178434 http://www.medworm.com/index.php?rid=4178433&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.148 Biological Chemistry 391 (12): 1379-1390 Abstract To defend against invading pathogens, plants possess RNA silencing mechanisms involving small RNAs (miRNAs, siRNAs). Also viroids – plant infectious, non-coding, unencapsidated RNA – cause the production of viroid-specific small RNAs (vsRNA), but viroids do escape the cytoplasmic silencing mechanism. Viroids with minor sequence variations can produce different symptoms in infected plants, suggesting an involvement of vsRNAs in symptom production. We analyzed by deep sequencing the spectrum of vsRNAs induced by the PSTVd strain AS1, which causes strong symptoms such as dwarfing and necrosis upon infection of tomato plants cv Rutgers. Indeed, vsRNAs found with highest frequency mapped to the pathogenicity-modulating domain of PSTVd, suppo... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4178433 Thu, 18 Nov 2010 17:09:56 +0100 4178433 http://www.medworm.com/index.php?rid=4178432&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.144 Biological Chemistry 391 (12): 1371-1378 Abstract Aldo-keto reductase family 1 member B10 (AKR1B10), over-expressed in multiple human cancers, might be implicated in cancer development and progression via detoxifying cytotoxic carbonyls and regulating fatty acid synthesis. In the present study, we investigated the ortholog of AKR1B10 in mice, an ideal modeling organism greatly contributing to human disease investigations. In the mouse, there are three aldo-keto reductase family 1 subfamily B (AKR1B) members, i.e., AKR1B3, AKR1B7, and AKR1B8. Among them, AKR1B8 has the highest similarity to human AKR1B10 in terms of amino acid sequence, computer-modeled structures, substrate spectra and specificity, and tissue distribution. More importantly, similar to human AKR1B10, mouse AKR1B8 associates... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4178432 Thu, 18 Nov 2010 17:09:56 +0100 4178432 http://www.medworm.com/index.php?rid=4178431&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.149 Biological Chemistry 391 (12): 1365-1370 Abstract The TNF family molecule RANKL and its receptor RANK are key regulators of bone remodeling, lymph node formation, and mammary gland development during pregnancy. RANKL and RANK are also expressed in the central nervous systems (CNS). However, the functional relevance of RANKL/RANK in the brain was entirely unknown. Recently, our group reported that the RANKL/RANK signaling pathway has an essential role in the central regulation of body temperature via the prostaglandin axis. This review discusses novel aspects of the RANKL/RANK system as key regulators of fever and female basal body temperature in the CNS. (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4178431 Thu, 18 Nov 2010 17:09:56 +0100 4178431 http://www.medworm.com/index.php?rid=4182349&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.142 Biological Chemistry 391 (11): 1233-1234 No abstract available (Source: Biological Chemistry) Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4182349 Mon, 01 Nov 2010 00:00:00 +0100 4182349 http://www.medworm.com/index.php?rid=4116549&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.116 Biological Chemistry 391 (10): 1221-1232 Abstract The glutamyl endopeptidase family of enzymes from staphylococci has been shown to be important virulence determinants of pathogenic family members, such as Staphylococcus aureus. Previous studies have identified the N-terminus and residues from positions 185–195 as potentially important regions that determine the activity of three members of the family. Cloning and sequencing of the new family members from Staphylococcus caprae (GluScpr) and Staphylococcus cohnii (GluScoh) revealed that the N-terminal Val residue is maintained in all family members. Mutants of the GluV8 enzyme from S. aureus with altered N-terminal residues, including amino acids with similar properties, were inactive, indicating that the Val residue is specifically requi... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4116549 Sat, 30 Oct 2010 00:16:14 +0100 4116549 http://www.medworm.com/index.php?rid=4116548&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.126 Biological Chemistry 391 (10): 1205-1219 Abstract To assess the significance of the non-genomic signaling of TCDD (=dioxin) on liver of C57BL/6 mice and HepG2 human hepatoma cells, we first determined the group of markers that are susceptible to inhibition by parthenolide, a compound known to specifically suppress NF-κB-mediated inflammation. Of those, the most consistent marker turned out to be SOCS3 (a suppressor of cytokine signaling) known to respond to inflammation. An early diagnostic test on the action of TCDD on HepG2 cells in vitro within 3–6 h indicated that Cox-2 and SOCS3 are mainly induced via a non-genomic route, whereas PAI-2 appears to be induced through the classical action route. More detailed diagnostic tests at later stages of action of TCDD in HepG2 cells revealed ... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4116548 Sat, 30 Oct 2010 00:16:14 +0100 4116548 http://www.medworm.com/index.php?rid=4116547&cid=s_36294_59_f&fid=36294&url=http%3A%2F%2Fwww.reference-global.com%2Fdoi%2Fabs%2F10.1515%2FBC.2010.121 Biological Chemistry 391 (10): 1197-1203 Abstract Selective permeability for small proteins and oligopeptides occurs in the intestinal epithelium of many animal species and humans. Whole proteins are sometimes endocytosed and undergo partial hydrolysis in intestinal epithelial cells with the probable release of essential oligopeptides into the bloodstream. Increased permeability to certain proteins can cause asthma and other metabolic disorders. Permeable proteins have also been successfully used to deliver vaccines or drugs via oral consumption. Protein absorption has been inferred in many cases and demonstrated in some cases by histochemical, tracer, and analytical techniques. However, the nature and importance of protein absorption remains largely unknown. Here, we demonstrate the movem... Biological Chemistry journals http://www.medworm.com/rss/comments.php?id=4116547 Sat, 30 Oct 2010 00:16:14 +0100 4116547