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).
Antioxidants & Redox Signaling
Mostrando recursos 1 - 20 de 760
miRNA-30 Family Inhibition Protects Against Cardiac Ischemic Injury by Regulating Cystathionine-γ-Lyase Expression - Shen, Yaqi; Shen, Zhuqing; Miao, Lei; Xin, Xiaoming; Lin, Shizhou; Zhu, Yichun; Guo, Wei; Zhu, Yi Zhun
Aims: Myocardial infarction (MI) is a leading cause of death globally. MicroRNAs (miRNAs) have been identified as a novel class of MI injury regulators. Hydrogen sulfide (H2S) is a gaseous signaling molecule that regulates cardiovascular function. The purpose of this study was to explore the role of the miR-30 family in protecting against MI injury by regulating H2S production. Results: The expression of miR-30 family was upregulated in the murine MI model as well as in the primary cardiomyocyte hypoxic model. However, the cystathionine-γ-lyase (CSE) expression was significantly decreased. The overexpression of miR-30 family decreased CSE expression, reduced H2S production,...
Evolutionary Acquisition of Cysteines Determines FOXO Paralog-Specific Redox Signaling - Putker, Marrit; Vos, Harmjan R.; van Dorenmalen, Kim; de Ruiter, Hesther; Duran, Ana G.; Snel, Berend; Burgering, Boudewijn M.T.; Vermeulen, Michiel; Dansen, Tobias B.
Reduction–oxidation (redox) signaling, the translation of an oxidative intracellular environment into a cellular response, is mediated by the reversible oxidation of specific cysteine thiols. The latter can result in disulfide formation between protein hetero- or homodimers that alter protein function until the local cellular redox environment has returned to the basal state. We have previously shown that this mechanism promotes the nuclear localization and activity of the Forkhead Box O4 (FOXO4) transcription factor. Aims: In this study, we sought to investigate whether redox signaling differentially controls the human FOXO3 and FOXO4 paralogs. Results: We present evidence that FOXO3 and FOXO4...
Redox-Sensitive Structure and Function of the First Extracellular Loop of the Cell–Cell Contact Protein Claudin-1: Lessons from Molecular Structure to Animals - Dabrowski, Sebastian; Staat, Christian; Zwanziger, Denise; Sauer, Reine-Solange; Bellmann, Christian; Günther, Ramona; Krause, Eberhard; Haseloff, Reiner Fritz; Rittner, Heike; Blasig, Ingolf Ernst
The paracellular cleft within epithelia/endothelia is sealed by tight junction (TJ) proteins. Their extracellular loops (ECLs) are assumed to control paracellular permeability and are targets of pathogenes. We demonstrated that claudin-1 is crucial for paracellular tightening. Its ECL1 is essential for the sealing and contains two cysteines conserved throughout all claudins. Aims: We prove the hypothesis that this cysteine motif forms a redox-sensitive intramolecular disulfide bridge and, hence, the claudin-1-ECL1 constitutes a functional structure which is associated to ECLs of this and other TJ proteins. Results: The structure and function of claudin-1-ECL1 was elucidated by investigating sequences of this ECL...
Emerging Concepts in Hypertension - Francis, Joseph; Davisson, Robin L.
Cellular redox balance is vital in health and disease. In this Forum, we highlight the importance of reactive oxygen species (ROS) in the regulation of redox balance in different organ systems of the body and ROS contribution to the development of hypertension. The Forum examines interactions between oxidative and nitrosative stress in the brain, vasculature, and kidney, and redox effect on end-organ damage and hypertension. Furthermore, the Forum examines the role of immune cells in the modulation of hypertension. We also introduce a new role for endoplasmic reticulum stress in the induction of ROS and its possible contribution to the...
Endoplasmic Reticulum Stress and Nox-Mediated Reactive Oxygen Species Signaling in the Peripheral Vasculature: Potential Role in Hypertension - Santos, Celio X.C.; Nabeebaccus, Adam A.; Shah, Ajay M.; Camargo, Livia L.; Filho, Sidney V.; Lopes, Lucia R.
Significance: Reactive oxygen species (ROS) are produced during normal endoplasmic reticulum (ER) metabolism. There is accumulating evidence showing that under stress conditions such as ER stress, ROS production is increased via enzymes of the NADPH oxidase (Nox) family, especially via the Nox2 and Nox4 isoforms, which are involved in the regulation of blood pressure. Hypertension is a major contributor to cardiovascular and renal disease, and it has a complex pathophysiology involving the heart, kidney, brain, vessels, and immune system. ER stress activates the unfolded protein response (UPR) signaling pathway that has prosurvival and proapoptotic components. Recent Advances: Here, we summarize...
Oxidative Stress in Hypertension: Role of the Kidney - Araujo, Magali; Wilcox, Christopher S.
Significance: Renal oxidative stress can be a cause, a consequence, or more often a potentiating factor for hypertension. Increased reactive oxygen species (ROS) in the kidney have been reported in multiple models of hypertension and related to renal vasoconstriction and alterations of renal function. Nicotinamide adenine dinucleotide phosphate oxidase is the central source of ROS in the hypertensive kidney, but a defective antioxidant system also can contribute. Recent Advances: Superoxide has been identified as the principal ROS implicated for vascular and tubular dysfunction, but hydrogen peroxide (H2O2) has been implicated in diminishing preglomerular vascular reactivity, and promoting medullary blood flow...
Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research - Montezano, Augusto C.; Touyz, Rhian M.
Significance: Reactive oxygen species (ROS) are signaling molecules that are important in physiological processes, including host defense, aging, and cellular homeostasis. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in the onset and/or progression of chronic diseases, including hypertension. Recent Advances: Although oxidative stress may not be the only cause of hypertension, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors, such as salt loading, activation of the renin-angiotensin-aldosterone system, and sympathetic hyperactivity, at least in experimental models. A major source for ROS in the cardiovascular-renal system is a family of nicotinamide adenine...
Fasting Induces Nuclear Factor E2-Related Factor 2 and ATP-Binding Cassette Transporters via Protein Kinase A and Sirtuin-1 in Mouse and Human - Kulkarni, Supriya R.; Donepudi, Ajay C.; Xu, Jialin; Wei, Wei; Cheng, Qiuqiong C.; Driscoll, Maureen V.; Johnson, Delinda A.; Johnson, Jeffrey A.; Li, Xiaoling; Slitt, Angela L.
Aims: The purpose of this study was to determine whether 3′-5′-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) and Sirtuin-1 (SIRT1) dependent mechanisms modulate ATP-binding Cassette (ABC) transport protein expression. ABC transport proteins (ABCC2–4) are essential for chemical elimination from hepatocytes and biliary excretion. Nuclear factor-E2 related-factor 2 (NRF2) is a transcription factor that mediates ABCC induction in response to chemical inducers and liver injury. However, a role for NRF2 in the regulation of transporter expression in nonchemical models of liver perturbation is largely undescribed. Results: Here we show that fasting increased NRF2 target gene expression through NRF2- and SIRT1–dependent mechanisms....
Hydrogen Sulfide Attenuates Opioid Dependence by Suppression of Adenylate Cyclase/cAMP Pathway - Yang, Hai-Yu; Wu, Zhi-Yuan; Wood, Mark; Whiteman, Matthew; Bian, Jin-Song
Aims: The best-established mechanism of opioid dependence is the up-regulation of adenylate cyclase (AC)/cAMP pathway, which was reported to be negatively regulated by hydrogen sulfide (H2S), a novel endogenous neuromodulator. The present study was, therefore, designed to determine whether H2S is able to attenuate the development of opioid dependence via down-regulating AC/cAMP pathway. Results: We demonstrated that application of sodium hydrosulphide (NaHS) and GYY4137, two donors of H2S, significantly alleviated naloxone-induced robust withdrawal jumping (the most sensitive and reliable index of opioid physical dependence) in morphine-treated mice. Repeated treatment with NaHS inhibited the up-regulated protein expression of AC in the...
The Cooperative Roles of Inflammation and Oxidative Stress in the Pathogenesis of Hypertension - Crowley, Steven D.
Significance: Innate and adaptive immunity play fundamental roles in the development of hypertension and its complications. As effectors of the cell-mediated immune response, myeloid cells and T lymphocytes protect the host organism from infection by attacking foreign intruders with bursts of reactive oxygen species (ROS). Recent Advances: While these ROS may help to preserve the vascular tone and thereby protect against circulatory collapse in the face of overwhelming infection, aberrant elaboration of ROS triggered by immune cells in the absence of a hemodynamic insult can lead to pathologic increases in blood pressure. Conversely, misdirected oxidative stress in cardiovascular control organs,...
Hypoxia-Responsive MicroRNA-101 Promotes Angiogenesis via Heme Oxygenase-1/Vascular Endothelial Growth Factor Axis by Targeting Cullin 3 - Kim, Ji-Hee; Lee, Kwang-Soon; Lee, Dong-Keon; Kim, Joohwan; Kwak, Su-Nam; Ha, Kwon-Soo; Choe, Jongseon; Won, Moo-Ho; Cho, Byung-Ryul; Jeoung, Dooil; Lee, Hansoo; Kwon, Young-Guen; Kim, Young-Myeong
Aims: Hypoxia induces expression of various genes and microRNAs (miRs) that regulate angiogenesis and vascular function. In this study, we investigated a new functional role of new hypoxia-responsive miR-101 in angiogenesis and its underlying mechanism for regulating heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) expression. Results: We found that hypoxia induced miR-101, which binds to the 3′untranslated region of cullin 3 (Cul3) and stabilizes nuclear factor erythroid-derived 2-related factor 2 (Nrf2) via inhibition of the proteasomal degradation pathway. miR-101 overexpression promoted Nrf2 nuclear accumulation, which was accompanied with increases in HO-1 induction, VEGF expression, and endothelial nitric oxide...
Redox Pioneer: Professor Helmut Sies - Jones, Dean P.; Radi, Rafael
Dr. Helmut Sies (MD, 1967) is recognized as a Redox Pioneer, because he authored five articles on oxidative stress, lycopene, and glutathione, each of which has been cited more than 1000 times, and coauthored an article on hydroperoxide metabolism in mammalian systems cited more than 5000 times (Google Scholar). He obtained preclinical education at the University of Tübingen and the University of Munich, clinical training at Munich (MD, 1967) and Paris, and completed Habilitation at Munich (Physiological Chemistry and Physical Biochemistry, 1972). In early research, he first identified hydrogen peroxide (H2O2) as a normal aerobic metabolite and devised a method...
Thioredoxin-Interacting Protein Expression Is Required for VEGF-Mediated Angiogenic Signal in Endothelial Cells - Abdelsaid, Mohammed A.; Matragoon, Suraporn; El-Remessy, Azza B.
Aims: Thioredoxin-interacting protein (TXNIP) contributes to cellular redox-state homeostasis via binding and inhibiting thioredoxin (TRX). Increasing evidence suggests that cellular redox homeostasis regulates vascular endothelial growth factor (VEGF)-mediated signaling. This study aims to examine the redox-dependant role of TXNIP in regulating VEGF-mediated S-glutathionylation and angiogenic signaling. TXNIP-knockout mice (TKO) or wild-type (WT) treated with the reduced glutathione (GSH)-precursor, N-acetyl cysteine (WT-NAC, 500 mg/kg) were compared to WT using hypoxia-induced neovascularization model. Results: In response to hypoxia, retinas from TKO and WT-NAC mice showed significant decreases in reparative revascularization and pathological neovascularization with similar VEGF expression compared with WT. VEGF failed to...
Direct sGC Activation Bypasses NO Scavenging Reactions of Intravascular Free Oxy-Hemoglobin and Limits Vasoconstriction - Raat, Nicolaas J.H.; Tabima, D. Marcela; Specht, Patricia A.C.; Tejero, Jesús; Champion, Hunter C.; Kim-Shapiro, Daniel B.; Baust, Jeff; Mik, Egbert G.; Hildesheim, Mariana; Stasch, Johannes-Peter; Becker, Eva-Maria; Truebel, Hubert; Gladwin, Mark T.
Aims: Hemoglobin-based oxygen carriers (HBOC) provide a potential alternative to red blood cell (RBC) transfusion. Their clinical application has been limited by adverse effects, in large part thought to be mediated by the intravascular scavenging of the vasodilator nitric oxide (NO) by cell-free plasma oxy-hemoglobin. Free hemoglobin may also cause endothelial dysfunction and platelet activation in hemolytic diseases and after transfusion of aged stored RBCs. The new soluble guanylate cyclase (sGC) stimulator Bay 41-8543 and sGC activator Bay 60-2770 directly modulate sGC, independent of NO bioavailability, providing a potential therapeutic mechanism to bypass hemoglobin-mediated NO inactivation. Results: Infusions of human...