PubMed Central (PMC3 - NLM DTD)
Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).
Hypothalamic Apelin/Reactive Oxygen Species Signaling Controls Hepatic Glucose Metabolism in the Onset of Diabetes - Drougard, Anne; Duparc, Thibaut; Brenachot, Xavier; Carneiro, Lionel; Gouazé, Alexandra; Fournel, Audren; Geurts, Lucie; Cadoudal, Thomas; Prats, Anne-Catherine; Pénicaud, Luc; Vieau, Didier; Lesage, Jean; Leloup, Corinne; Benani, Alexandre; Cani, Patrice D.; Valet, Philippe; Knauf, Claude
Aims: We have previously demonstrated that central apelin is implicated in the control of peripheral glycemia, and its action depends on nutritional (fast versus fed) and physiological (normal versus diabetic) states. An intracerebroventricular (icv) injection of a high dose of apelin, similar to that observed in obese/diabetic mice, increase fasted glycemia, suggesting (i) that apelin contributes to the establishment of a diabetic state, and (ii) the existence of a hypothalamic to liver axis. Using pharmacological, genetic, and nutritional approaches, we aim at unraveling this system of regulation by identifying the hypothalamic molecular actors that trigger the apelin effect on liver...
Glutathione Peroxidase 7 Utilizes Hydrogen Peroxide Generated by Ero1α to Promote Oxidative Protein Folding - Wang, Lei; Zhang, Lihui; Niu, Yingbo; Sitia, Roberto; Wang, Chih-chen
Aims: Ero1 flavoproteins catalyze oxidative folding in the endoplasmic reticulum (ER), consuming oxygen and generating hydrogen peroxide (H2O2). The ER-localized glutathione peroxidase 7 (GPx7) shows protein disulfide isomerase (PDI)-dependent peroxidase activity in vitro. Our work aims at identifying the physiological role of GPx7 in the Ero1α/PDI oxidative folding pathway and at dissecting the reaction mechanisms of GPx7. Results: Our data show that GPx7 can utilize Ero1α-produced H2O2 to accelerate oxidative folding of substrates both in vitro and in vivo. H2O2 oxidizes Cys57 of GPx7 to sulfenic acid, which can be resolved by Cys86 to form an intramolecular disulfide bond. Both...
Redox Control of Cardiac Excitability - Aggarwal, Nitin T.; Makielski, Jonathan C.
Reactive oxygen species (ROS) have been associated with various human diseases, and considerable attention has been paid to investigate their physiological effects. Various ROS are synthesized in the mitochondria and accumulate in the cytoplasm if the cellular antioxidant defense mechanism fails. The critical balance of this ROS synthesis and antioxidant defense systems is termed the redox system of the cell. Various cardiovascular diseases have also been affected by redox to different degrees. ROS have been indicated as both detrimental and protective, via different cellular pathways, for cardiac myocyte functions, electrophysiology, and pharmacology. Mostly, the ROS functions depend on the type...
Do Globins in Microaerophilic Campylobacter jejuni Confer Nitrosative Stress Tolerance Under Oxygen Limitation? - Avila-Ramirez, Carlos; Tinajero-Trejo, Mariana; Davidge, Kelly S.; Monk, Claire E.; Kelly, David J.; Poole, Robert K.
The microaerophilic pathogen Campylobacter jejuni possesses inducible systems for resisting NO. Two globins—Cgb (a single-domain globin) and Ctb (a truncated globin)—are up-regulated in response to NO via the positively acting transcription factor NssR. Our aims were to determine whether these oxygen-binding globins also function in severely oxygen-limited environments, as in the host. At growth-limiting oxygen transfer rates, bacteria were more S-nitrosoglutathione (GSNO) sensitive, irrespective of the presence of Cgb, Ctb, or NssR. Pregrowth of cells with GSNO enhanced GSNO resistance, even in nssR and cgb mutants, but transcriptomic profiling of oxygen-limited, NO-exposed cells failed to reveal the NssR regulon. Nevertheless,...
Carbon Monoxide Signaling in Human Red Blood Cells: Evidence for Pentose Phosphate Pathway Activation and Protein Deglutathionylation - Metere, Alessio; Iorio, Egidio; Scorza, Giuseppe; Camerini, Serena; Casella, Marialuisa; Crescenzi, Marco; Minetti, Maurizio; Pietraforte, Donatella
Aims: The biochemistry underlying the physiological, adaptive, and toxic effects of carbon monoxide (CO) is linked to its affinity for reduced transition metals. We investigated CO signaling in the vasculature, where hemoglobin (Hb), the CO most important metal-containing carrier is highly concentrated inside red blood cells (RBCs). Results: By combining NMR, MS, and spectrophotometric techniques, we found that CO treatment of whole blood increases the concentration of reduced glutathione (GSH) in RBC cytosol, which is linked to a significant Hb deglutathionylation. In addition, this process (i) does not activate glycolytic metabolism, (ii) boosts the pentose phosphate pathway (PPP), (iii) increases...
Keratinocyte Growth Factor and Glucocorticoid Induction of Human Peroxiredoxin 6 Gene Expression Occur by Independent Mechanisms That Are Synergistic - Chowdhury, Ibrul; Fisher, Aron B.; Christofidou-Solomidou, Melpo; Gao, Ling; Tao, Jain-Qin; Sorokina, Elena M.; Lien, Yu-Chin; Bates, Sandra R.; Feinstein, Sheldon I.
Aims: Peroxiredoxin 6 (Prdx6), a 1-cys Prdx has both peroxidase and phospholipase A2 activities, protecting against oxidative stress and regulating pulmonary surfactant phospholipid metabolism. This study determined the mechanism by which keratinocyte growth factor (KGF) and the glucocorticoid analogue, dexamethasone (Dex), induce increased Prdx6 expression. Results: Transcriptional activation by KGF in both A549 lung adenocarcinoma cells and rat lung alveolar epithelial type II (ATII) cells utilizes an antioxidant response element (ARE), located between 357 and 349 nucleotides before the PRDX6 translational start, that is also necessary for upregulation of the human PRDX6 promoter in response to oxidative stress. Activation is...
Advanced Oxidation Protein Products Activate Intrarenal Renin–Angiotensin System via a CD36-Mediated, Redox-Dependent Pathway - Cao, Wei; Xu, Jie; Zhou, Zhan Mei; Wang, Guo Bao; Hou, Fan Fan; Nie, Jing
Aims: Activation of intrarenal renin–angiotensin system (RAS) has a detrimental effect on the progression of chronic kidney diseases (CKDs), although the regulation of intrarenal RAS remains unclear. The aim of the present study was to evaluate the role of advanced oxidation protein products (AOPPs) in intrarenal RAS activation. Results: AOPPs upregulated the expression of almost all components of RAS and increased activity of angiotensin-converting enzyme in cultured proximal tubular epithelial cells. The triggering effect of AOPP-albumin was 100-times stronger than that of unmodified albumin. The effect of AOPP-albumin was mainly mediated by a CD36-dependent, redox-sensitive signaling involving activation of protein...