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Antioxidants & Redox Signaling

Xiaoyuan Ren, Lili Zou, Xu Zhang, Vasco Branco, Jun Wang, Cristina Carvalho, Arne Holmgren, Jun Lu
SIGNIFICANCE: The thioredoxin (Trx) and glutathione (GSH) systems play important roles in maintaining the redox balance in the brain, a tissue that is prone to oxidative stress due to its high energy demand. These two disulfide reductase systems are active in various areas of the brain, and are considered to be the critical antioxidant systems in the central nervous system (CNS). Various neuronal disorders have been characterized to have imbalanced redox homeostasis. Recent Advances: In addition to their detrimental effects, recent studies have highlighted that reactive oxygen/nitrogen species (ROS/RNS) act as critical signaling molecules by modifying thiols in proteins...
April 26, 2017: Antioxidants & Redox Signaling
Andrea K Steiger, Yu Zhao, Michael D Pluth
SIGNIFICANCE: Carbonyl sulfide (COS) is the most prevalent sulfur-containing gas in Earth's atmosphere and plays important roles in the global sulfur cycle. COS has been implicated in origin of life peptide ligation, is the primary energy source for certain bacteria, and has been detected in mammalian systems. Despite this long and intertwined history with terrestrial biology, limited attention has focused on potential roles of COS as a biological mediator. Recent Advances. Although bacterial COS production is well documented, definitive sources of mammalian COS production have not been confirmed...
April 26, 2017: Antioxidants & Redox Signaling
Yoko Takano, Honami Echizen, Kenjiro Hanaoka
SIGNIFICANCE: Hydrogen sulfide (H2S) plays roles in many physiological processes, including relaxation of vascular smooth muscles, mediation of neurotransmission, inhibition of insulin signaling, and regulation of inflammation. Also, hydropersulfide (R-S-SH) and polysulfide (-S-Sn-S-) have recently been identified as reactive sulfur species (RSS) that regulate the bioactivities of multiple proteins via S-sulfhydration of cysteine residues (protein Cys-SSH) and show the cytoprotection...
April 26, 2017: Antioxidants & Redox Signaling
Ying Shao, Gayani Nanayakkara, Jiali Cheng, Ramon Cueto, William Y Yang, Joon-Young Park, Hong Wang, Xiaofeng Yang
SIGNIFICANCE: We proposed lysophospholipids (LPLs) and LPL-G-protein-coupled receptors (GPCRs) as conditional danger-associated molecular patterns (DAMPs) and conditional DAMP receptors as a paradigm shift to the widely accepted classical DAMP and DAMP receptor model. Recent Advances: The aberrant levels of LPLs and GPCRs activate pro-inflammatory signal transduction pathways, trigger innate immune response, and lead to tissue oxidative and inflammatory injury. CRITICAL ISSUES: Classical DAMP model specifies only the endogenous metabolites that are released from damaged/dying cells as DAMPs, but fails to identify elevated endogenous metabolites secreted from viable/live cells during pathologies as DAMPs...
April 26, 2017: Antioxidants & Redox Signaling
George J Dugbartey, Maarten C Hardenberg, Wendelinde F Kok, Ate S Boerema, Hannah V Carey, James F Staples, Robert H Henning, Hjalmar R Bouma
SIGNIFICANCE: Therapeutic hypothermia is commonly applied to limit ischemic injury in organ transplantation, during cardiac and brain surgery and after cardiopulmonary resuscitation. In these procedures, the kidneys are particularly at risk for ischemia/reperfusion injury (IRI), likely due to their high rate of metabolism. Although hypothermia mitigates ischemic kidney injury, it is not a panacea. Residual mitochondrial failure is believed to be a key event triggering loss of cellular homeostasis, and potentially cell death...
April 26, 2017: Antioxidants & Redox Signaling
Pete Chandrangsu, Vu Van Loi, Haike Antelmann, John D Helmann
SIGNIFICANCE: Since the discovery and structural characterization of bacillithiol (BSH), the biochemical functions of BSH-biosynthesis enzymes (BshA/B/C) and BSH-dependent detoxification enzymes (FosB, Bst, GlxA/B) have been explored in Bacillus and Staphylococcus species. It was shown that BSH plays an important role in detoxification of reactive oxygen and electrophilic species, alkylating agents, toxins, and antibiotics. Recent Advances: More recently, new functions of BSH were discovered in metal homeostasis (Zn buffering, Fe-sulfur cluster, and copper homeostasis) and virulence control in Staphylococcus aureus...
April 24, 2017: Antioxidants & Redox Signaling
Hua Su, Cheng Wan, Chun-Tao Lei, Chun-Yun Zhang, Chen Ye, Hui Tang, Yue Qiu, Chun Zhang
SIGNIFICANCE: The relationship between lipid disturbances and renal diseases has been studied for several decades, and it is well recognized that when the balance of renal lipid uptake, synthesis, oxidation, and outflow is disrupted, lipids will undergo oxidation, be sequestrated as lipid droplets, generate toxic metabolites, and cause nephrotoxicity in diverse renal diseases. Recent Advances: During renal disorders, redox signaling is a pivotal event promoting or resulting from lipid disorders...
April 20, 2017: Antioxidants & Redox Signaling
Xuehong Liu, Catherine M Davis, Nabil J Alkayed
SIGNIFICANCE: Eicosanoids are endogenous lipid mediators that play important roles in brain function and disease. Acute brain injury such as that which occurs in stroke and traumatic brain injury increases the formation of eicosanoids, which, in turn, exacerbate or diminish injury. In chronic neurodegenerative diseases such as Alzheimer's disease and vascular dementia (VD), eicosanoid synthetic and metabolizing enzymes are altered, disrupting the balance between neuroprotective and neurotoxic eicosanoids...
April 20, 2017: Antioxidants & Redox Signaling
Christopher H Mauney, LeAnn C Rogers, Reuben S Harris, Larry W Daniel, Nelmi O Devarie-Baez, Hanzhi Wu, Cristina M Furdui, Leslie B Poole, Fred W Perrino, Thomas Hollis
AIMS: Proliferative signaling involves reversible posttranslational oxidation of proteins. However, relatively few molecular targets of these modifications have been identified. We investigate the role of protein oxidation in regulation of SAMHD1 catalysis. RESULTS: Here we report that SAMHD1 is a major target for redox regulation of nucleotide metabolism and cell cycle control. SAMHD1 is a triphosphate hydrolase, whose function involves regulation of deoxynucleotide triphosphate pools...
April 18, 2017: Antioxidants & Redox Signaling
Quan Jiang, Yinping Gao, Chengkun Wang, Rongrong Tao, Yan Wu, Kaiyu Zhan, Meihua Liao, Nannan Lu, Yingmei Lu, Christopher S Wilcox, Jianhong Luo, Lin-Hua Jiang, Wei Yang, Feng Han
AIMS: Dysfunction of neurovascular pericytes underlies breakdown of the blood-brain barrier, but the molecular mechanisms are largely unknown. In this study, we evaluated the role of the transient receptor potential melastatin-related 2 (TRPM2) channel and autophagy during brain pericyte injury both in vitro and in vivo. RESULTS: A rapid induction in autophagy in human brain vascular pericytes, in the zinc oxide nanoparticles (ZnO-NP)-induced cell stress model, was paralleled with an increase in the expression of the TRPM2-S truncated isoform, which was abolished by treatment with a nitric oxide synthase inhibitor and a peroxynitrite scavenger...
April 18, 2017: Antioxidants & Redox Signaling
Edgar Djaha Yoboue, Alessandro Rimessi, Tiziana Anelli, Paolo Pinton, Roberto Sitia
Glutathione peroxidases (GPXs) are enzymes that are present in almost all organisms with the primary function of limiting peroxide accumulation. In mammals, two of the eight members (GPX7 and GPX8) reside in the endoplasmic reticulum (ER). A peculiar feature of GPX8 is the concomitant presence of a conserved N-terminal transmembrane domain (TMD) and a C-terminal KDEL-like motif for ER localization. AIMS: Investigating whether and how GPX8 impacts Ca(2+) homeostasis and signaling. RESULTS: We show that GPX8 is enriched in mitochondria-associated membranes and regulates Ca(2+) storage and fluxes...
April 17, 2017: Antioxidants & Redox Signaling
Alexander S Keller, Brant E Isakson
Heterocellular communication between different cell types of the vasculature, both within the blood vessel wall and cells interacting with the blood vessel wall, is absolutely vital and must be tightly regulated. In this Forum, the role of four different gaseous transmitters [nitric oxide [NO], carbon monoxide (CO), hydrogen sulfide (H2S), and superoxide (O2(•-))] is examined by four different research groups in detail, with two original articles and two reviews of the literature. In this editorial, we discuss how each of them may contribute their own component to heterocellular signaling in the vasculature...
April 14, 2017: Antioxidants & Redox Signaling
Cristina Sánchez-Ramos, Ignacio Prieto, Alberto Tierrez, Javier Laso, M Pilar Valdecantos, Ramon Bartrons, Joan Roselló-Catafau, María Monsalve
AIMS: Liver steatosis is associated with mitochondrial dysfunction and elevated reactive oxygen species (ROS) levels together with enhanced sensitivity to ischemia-reperfusion (IR) injury and limited response to preconditioning protocols. Here, we sought to determine whether the downregulation in the steatotic liver of peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), a master regulator of mitochondrial metabolism and ROS that is known to play a role in liver metabolic control, could be responsible for the sensitivity of the steatotic liver to ischemic damage...
April 14, 2017: Antioxidants & Redox Signaling
Faraz Ahmad, Kunal Singh, Debajyoti Das, Ruturaj Gowaikar, Eisha Shaw, Arathy Ramachandran, Khader Valli Rupanagudi, Reddy Peera Kommaddi, David A Bennett, Vijayalakshmi Ravindranath
AIMS: Synaptic deficits are known to underlie the cognitive dysfunction seen in Alzheimer's disease (AD). Generation of reactive oxygen species (ROS) by β-amyloid has also been implicated in AD pathogenesis. However, it is unclear whether ROS contributes to synaptic dysfunction seen in AD pathogenesis and, therefore, we examined whether altered redox signaling could contribute to synaptic deficits in AD. RESULTS: Activity dependent but not basal translation was impaired in synaptoneurosomes from 1-month old presymptomatic APP(Swe)/PS1ΔE9 (APP/PS1) mice, and this deficit was sustained till middle age (MA, 9-10 months)...
April 12, 2017: Antioxidants & Redox Signaling
Lucia Alvarez, Christopher L Bianco, John P Toscano, Joseph Lin, Takaaki Akaike, Jon Fukuto
SIGNIFICANCE: For over 20 years the physiological signaling associated with the endogenous generation of hydrogen sulfide (H<sub>2</sub>S) has been of significant interest. In spite of its presumed importance, the biochemical mechanisms associated with its actions have not been elucidated. Recent Advances: Recently it has been found that H<sub>2</sub>S-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 H<sub>2</sub>S...
April 11, 2017: Antioxidants & Redox Signaling
Carlo Gabriele Tocchetti, Christian Cadeddu, Daniela Di Lisi, Saveria Femminò, Rosalinda Madonna, Donato Mele, Ines Monte, Giuseppina Novo, Claudia Penna, Alessia Pepe, Paolo Spallarossa, Gilda Varricchi, Concetta Zito, Pasquale Pagliaro, Giuseppe Mercuro
SIGNIFICANCE: Antineoplastic therapies have improved the prognosis of oncology patients sig-nificantly. However, these treatments can bring to a higher incidence of side effects, including the worrying cardiovascular toxicity (CTX). Recent Advances: Substantial evidence indicates multiple mechanisms of CTX, with redox mechanisms playing a key role. Recent data singled out mitochondria as key targets for antineoplastic drug-induced CTX; understanding the underlying mechanisms is therefore cru-cial for effective cardioprotection, without compromising the efficacy of anti-cancer treat-ments...
April 11, 2017: Antioxidants & Redox Signaling
Roberta d'Emmanuele di Villa Bianca, Ferdinando Fusco, Vincenzo Mirone, Giuseppe Cirino, Raffaella Sorrentino
Significance The endogenous hydrogen sulfide (H<sub></sub>2<sub></sub>S) pathway produces an array of biological effects that vary depending upon the bodily region. In addition, the H<sub></sub>2<sub></sub>S pathway's relevance often changes depending upon a healthy or disease state. There is abundant evidence pointing to a key role for this pathway in male and female genito-urinary diseases suggesting it as a possible target for new therapeutic approaches. Recent Advances The tissue-specific localization of the H2S enzymes in the genito-urinary tract has allowed for a better understanding of its role in the body's pathophysiology...
April 11, 2017: Antioxidants & Redox Signaling
Shuai Yuan, XInggui Shen, Christopher G Kevil
SIGNIFICANCE: Hydrogen sulfide 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 gamma lyase (CSE) and cystathionine beta synthase (CBS)...
April 11, 2017: Antioxidants & Redox Signaling
Miriam Margherita Cortese-Krott, Anne Koning, Gunter Georg Kuhnle, Peter Nagy, Christopher Bianco, Andreas Pasch, David A Wink, Jon 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 our current understanding of the underlying regulatory processes is incomplete. Recent Advances. Similar to reactive oxygen and nitrogen species (ROS, RNS), reactive sulfur species (RSS) are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism and mitochondrial function...
April 11, 2017: Antioxidants & Redox Signaling
Oded Rimon, Ohad Suss, Mor Goldenberg, Rosi Fassler, Ohad Yogev, Hadar Amartely, Guy Propper, Assaf Friedler, Dana Reichmann
AIMS: A recently discovered group of conditionally disordered chaperones share a very unique feature; they need to lose structure to become active as chaperones. This activation mechanism makes these chaperones particularly suited to respond to protein-unfolding stress conditions, such as oxidative unfolding. However, the role of this disorder in stress-related activation, chaperone function, and the crosstalk with other chaperone systems is not yet clear. Here, we focus on one of the members of the conditionally disordered chaperones, a thiol-redox switch of the bacterial proteostasis system, Hsp33...
April 10, 2017: Antioxidants & Redox Signaling
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