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Antioxidants & Redox Signaling

Xiaoyu Wang, Michael Hausding, Shih-Yen Weng, Yong Ook Kim, Sebastian Steven, Thomas Klein, Andreas Daiber, Detlef Schuppan
AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, panlobular inflammation, liver fibrosis and increased cardiovascular mortality. Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are indirect glucagon like peptide 1 (GLP-1) agonists with antidiabetic and anti-inflammatory activity, used for the treatment of type 2 diabetes. Their potential and underlying mechanisms to treat metabolic liver inflammation and fibrosis as well as the associated vascular dysfunction remain to be explored...
June 21, 2017: Antioxidants & Redox Signaling
Joshua P Fessel, William M Oldham
SIGNIFICANCE: Pyridine dinucleotides, NAD and NADP, were discovered over 100 years ago as necessary cofactors for fermentation in yeast extracts. Since that time, these molecules have been recognized as fundamental players in a variety of cellular processes, including energy metabolism, redox homeostasis, cellular signaling, and gene transcription, among many others. Given their critical role as mediators of cellular responses to metabolic perturbations, it is unsurprising that dysregulation of NAD and NADP metabolism has been associated with the pathobiology of many chronic human diseases...
June 21, 2017: Antioxidants & Redox Signaling
Pietro Ghezzi, Luciano Floridi, Diana Boraschi, Antonio Cuadrado, Gina Manda, Snezana Levic, Fulvio D'Acquisto, Alice Hamilton, Toby J Athersuch, Liza Selley
SIGNIFICANCE: The environment can elicit biological responses such as oxidative stress (OS) and inflammation as a consequence of chemical, physical, or psychological changes. As population studies are essential for establishing these environment-organism interactions, biomarkers of OS or inflammation are critical in formulating mechanistic hypotheses. Recent Advances: By using examples of stress induced by various mechanisms, we focus on the biomarkers that have been used to assess OS and inflammation in these conditions...
June 15, 2017: Antioxidants & Redox Signaling
Lucía Álvarez, Christopher L Bianco, John P Toscano, Joseph Lin, Takaaki Akaike, Jon M Fukuto
SIGNIFICANCE: For >20 years, physiological signaling associated with the endogenous generation of hydrogen sulfide (H2S) has been of significant interest. Despite its presumed importance, the biochemical mechanisms associated with its actions have not been elucidated. Recent Advances: Recently it has been found that H2S-related or derived species are highly prevalent in mammalian systems and that these species may be responsible for some, if not the majority, of the biological actions attributed to H2S...
June 13, 2017: Antioxidants & Redox Signaling
Celien Lismont, Marcus Nordgren, Chantal Brees, Bernard Knoops, Paul P Van Veldhoven, Marc Fransen
<b><i>Aims:</i></b> Peroxisomes are ubiquitous, single membrane-bounded organelles that contain considerable amounts of enzymes involved in the production or breakdown of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), a key signaling molecule in multiple biological processes and disease states. Despite this, the role of this organelle in cross-compartmental H<sub>2</sub>O<sub>2</sub> signaling remains largely unclear, mainly because of the difficulty to modulate peroxisomal H<sub>2</sub>O<sub>2</sub> production in a selective manner...
June 8, 2017: Antioxidants & Redox Signaling
Linlin Shi, Chenyang Zhao, Hongyun Wang, Tong Lei, Shasha Liu, Jianwei Cao, Zhongbing Lu
AIMS: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is mainly degraded by dimethylarginine dimethylaminohydrolase (DDAH). Emerging evidence suggests that plasma ADMA accumulation and DDAH1 activity/expression reduction are linked to chronic kidney disease (CKD) pathology, but the mechanisms remain largely unknown. Here, we examined the role of ADMA/DDAH1 in the epithelial-mesenchymal transition (EMT) of tubular epithelial cells (TECs), an important mechanism for the pathogenesis of renal fibrosis...
June 8, 2017: Antioxidants & Redox Signaling
Michael Liebthal, Daniel Maynard, Karl-Josef Dietz
SIGNIFICANCE: Peroxiredoxins (Prx) are thiol peroxidases with multiple functions in the antioxidant defense and redox signaling network of the cell. Our progressing understanding assigns both local and global significance to plant Prxs which are grouped in four Prx types. In plants they are localized to the cytosol, mitochondrion, plastid and nucleus. Antioxidant defense is fundamentally connected to redox signaling, cellular communication and acclimation. The thiol-disulfide network is central part of the stress sensing and processing response and integrates information input with redox regulation...
June 8, 2017: Antioxidants & Redox Signaling
Sarah Stöcker, Koen Van Laer, Ana Mijuskovic, Tobias P Dick
SIGNIFICANCE: H2O2 is known to act as a messenger in signal transduction. How H2O2 leads to selective and efficient oxidation of specific thiols on specific signaling proteins remains one of the most important open questions in redox biology. Recent Advances: Increasing evidence implicates thiol peroxidases as mediators of protein thiol oxidation. Recently, this evidence has been extended to include the peroxiredoxins. Peroxiredoxins are exceptionally sensitive to H2O2, abundantly expressed and capture most of the H2O2 that is generated inside cells...
June 6, 2017: Antioxidants & Redox Signaling
Sue Goo Rhee, Hyun Ae Woo, Dongmin Kang
Hydrogen peroxide (H2O2) is produced on stimulation of many cell surface receptors and serves as an intracellular messenger in the regulation of diverse physiological events, mostly by oxidizing cysteine residues of effector proteins. Mammalian cells express multiple H2O2-eliminating enzymes including catalase, glutathione peroxidase, and peroxiredoxin (Prx). A conserved cysteine in Prx family members is the site of oxidation by H2O2. Peroxiredoxins possess a high-affinity binding site for H2O2 that is lacking in catalase and glutathione peroxidase and which renders the catalytic cysteine highly susceptible to oxidation, with a rate constant several orders of magnitude greater than that for oxidation of cysteine in most H2O2 effector proteins...
June 6, 2017: Antioxidants & Redox Signaling
Gabriela Aguilera, Ana Laura Colín-González, Edgar Rangel-López, Anahí Chavarría, Abel Santamaría
SIGNIFICANCE: Production of pro-inflammatory and anti-inflammatory cytokines is part of the defense system that mostly microglia and macrophages display to induce normal signaling to counteract the deleterious actions of invading pathogens in the brain. Also, redox activity in the central nervous system (CNS) constitutes an integral part of the metabolic processes needed by cells to exert their normal molecular and biochemical functions. Under normal conditions, the formation of reactive oxygen and nitrogen species, and the following oxidative activity encounter a healthy balance with immunological responses to preserve cell functions in the brain...
June 6, 2017: Antioxidants & Redox Signaling
Miriam M Cortese-Krott, Anne Koning, Gunter G C Kuhnle, Peter Nagy, Christopher L Bianco, Andreas Pasch, David A Wink, Jon M Fukuto, Alan A Jackson, Harry van Goor, Kenneth R Olson, Martin Feelisch
SIGNIFICANCE: Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not, administration of antioxidants is ineffective, suggesting that our current understanding of the underlying regulatory processes is incomplete. Recent Advances: Similar to reactive oxygen species and reactive nitrogen species, reactive sulfur species are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism, and mitochondrial function...
June 6, 2017: Antioxidants & Redox Signaling
Noelia Diaz-Morales, Susana Rovira-Llopis, Celia Bañuls, Sandra Lopez-Domenech, Irene Escribano-Lopez, Silvia Veses, Ana Jover, Milagros Rocha, Antonio Hernandez-Mijares, Victor M Victor
Since metformin can exert beneficial vascular effects, we aimed at studying its effect on reactive oxygen species (ROS) production, antioxidant enzyme expression, levels of adhesion molecules, and leukocyte-endothelium interactions in the leukocytes from type 2 diabetic (T2D) patients. The study was carried out in 72 T2D patients (41 of whom were treated with metformin for at least 12 months at a dose of 1700 mg per day), and in 40 sex- and age-matched control subjects. Leukocytes from T2D patients exhibited enhanced levels of mitochondrial ROS and decreased mRNA levels of glutathione peroxidase 1 (gpx1) and sirtuin 3 (sirt3) with respect to controls, whereas metformin was shown to revert these effects...
June 2, 2017: Antioxidants & Redox Signaling
Outi Sareila, Cecilia Hagert, Tiina Kelkka, Marjo Linja, Bingze Xu, Jan Kihlberg, Rikard Holmdahl
AIMS: Neutrophil cytosolic factor 1 (NCF1) is a key regulatory component of the phagocytic NOX2 complex, which produces reactive oxygen species (ROS). Polymorphism of the Ncf1 gene is associated with increased arthritis severity. In this study, we generated targeted Ncf1 knock-in mice with inducible Ncf1 expression and determined the critical time window during which the NOX2-derived ROS protect the mice from arthritis. RESULTS: Targeted Ncf1 knock-in mice lacked NOX2-derived ROS, and in vivo allelic conversion of Ncf1 by the CreER(T2) recombinase led to full protein expression and ROS production within 10 days...
June 1, 2017: Antioxidants & Redox Signaling
Shuai Yuan, Xinggui Shen, Christopher G Kevil
SIGNIFICANCE: Hydrogen sulfide (H2S) metabolism leads to the formation of oxidized sulfide species, including polysulfide, persulfide, and others. Evidence is emerging that many biological effects of H2S may indeed be due to polysulfide and persulfide activation of signaling pathways and reactivity with discrete small molecules. Recent Advances: Exogenous oxidized sulfide species, including polysulfides, are more reactive than H2S with a wide range of molecules. Importantly, endogenous polysulfide and persulfide formation has been reported to occur via transsulfuration enzymes, cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS)...
June 1, 2017: Antioxidants & Redox Signaling
Verónica Miguel, Julia Yue Cui, Lidia Daimiel, Cristina Espinosa-Díez, Carlos Fernandez-Hernando, Terrance J Kavanagh, Santiago Lamas
SIGNIFICANCE: MicroRNAs (miRNAs) are important regulators of gene expression and define part of the epigenetic signature. Their influence on every realm of biomedicine is established and progressively increasing. The impact of environment on human health is enormous. Among environmental risk factors impinging on quality of life are those of chemical nature (toxic chemicals, heavy metals, pollutants, pesticides) as well as those related to everyday life such as exposure to noise or mental and psychosocial stress...
May 31, 2017: Antioxidants & Redox Signaling
Jasimuddin Ahamed, Jeffrey Laurence
SIGNIFICANCE: This review evaluates the role of platelet-derived TGF-β1 in oxidative stress-linked pathologic fibrosis, with an emphasis on the heart and kidney, using ionizing radiation as a clinically relevant stimulus. Current radiation-induced organ fibrosis interventions focus on pan-neutralization of transforming growth factor (TGF)-β1 or use of anti-oxidants and anti-proliferative agents, with limited clinical efficacy. Recent Advances: Pathologic fibrosis represents excessive accumulation of collagen and other extracellular matrix (ECM) components following dysregulation of a balance between ECM synthesis and degradation...
May 31, 2017: Antioxidants & Redox Signaling
Ashok Kumar, Brittney Yegla, Thomas C Foster
SIGNIFICANCE: Oxidative stress increases in the brain with aging and neurodegenerative diseases. Previous work emphasized irreversible oxidative damage in relation to cognitive impairment. This research has evolved to consider a continuum of alterations, from redox signaling to oxidative damage, which provides a basis for understanding the onset and progression of cognitive impairment. This review provides an update on research linking redox signaling to altered function of neural circuits involved in information processing and memory...
May 31, 2017: Antioxidants & Redox Signaling
Hideo Kimura
Hydrogen sulfide (H<sub>2</sub>S) has been demonstrated to have physiological roles such as neuromodulation, vascular tone regulation, cytoprotection, oxygen sensing, inflammatory regulation, and cell growth. Recently, hydrogen polysulfides (H<sub>2</sub>S<sub>n</sub>) have been found to be produced by 3-mercaptopyruvate sulfurtransferase (3MST) and to regulate the activity of ion channels, tumor suppressers, and protein kinases. Furthermore, some of the effects previously reported to be mediated by H<sub>2</sub>S are now ascribed to H<sub>2</sub>S<sub>n</sub>...
May 30, 2017: Antioxidants & Redox Signaling
Thomas Meyer, Petra H Wirtz
SIGNIFICANCE: Psychosocial stress is associated with alterations in serum glucocorticoids and cytokines, such as interleukin-6 (IL-6) and IL-1β, which functionally interact. However, the molecular mechanisms and physiological relationship between the two systems within the context of stress exposure are not well characterized. Recent Advances: Extracellular IL-6, which stimulates the release of cortisol from the zona fasciculata of the adrenal cortex, mediates its intracellular effects by tyrosine phosphorylation of the transcription factor STAT3 (signal transducer and activator of transcription 3)...
May 30, 2017: Antioxidants & Redox Signaling
Gaetano Calabrese, Bruce Morgan, Jan Riemer
SIGNIFICANCE: Mitochondrial glutathione fulfils crucial roles in a number of processes including iron-sulfur cluster biosynthesis and peroxide detoxification. Recent Advances: Genetically-encoded fluorescent probes for the glutathione redox potential (EGSH) have permitted extensive new insights into the regulation of mitochondrial glutathione redox homeostasis. These probes have revealed that the glutathione pools of the mitochondrial matrix and intermembrane space (IMS) are highly reduced, similar to the cytosolic glutathione pool...
May 30, 2017: Antioxidants & Redox Signaling
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