Oxidoreduction of protein thiols in redox regulation

2005 ◽  
Vol 33 (6) ◽  
pp. 1378-1381 ◽  
Author(s):  
P. Ghezzi
Keyword(s):  
Oxidative Stress ◽  
Redox State ◽  
Redox Regulation ◽  
Regulatory Mechanism ◽  
Protein Damage ◽  
The Past ◽  
Protein Thiols ◽  
Cellular Compartments

Protein cysteines can undergo various forms of oxidation, some of them reversible (disulphide formation, glutathionylation and S-nitrosylation). While in the past these were viewed as protein damage in the context of oxidative stress, there is growing interest in oxidoreduction of protein thiols/disulphides as a regulatory mechanism. This review discusses the evolution of the concept of redox regulation from that of oxidative stress and the redox state of protein cysteines in different cellular compartments.

scholarly journals Oxidative Stress in the Healthy and Wounded Hepatocyte: A Cellular Organelles Perspective

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Tommaso Mello ◽  
Francesca Zanieri ◽  
Elisabetta Ceni ◽  
Andrea Galli
Keyword(s):  
Oxidative Stress ◽  
Structural Damage ◽  
Redox State ◽  
Iron Homeostasis ◽  
Structural Integrity ◽  
Whole Body ◽  
Metabolic Demand ◽  
Research Activity ◽  
Cellular Compartments ◽  
Cellular Organelles

Accurate control of the cell redox state is mandatory for maintaining the structural integrity and physiological functions. This control is achieved both by a fine-tuned balance between prooxidant and anti-oxidant molecules and by spatial and temporal confinement of the oxidative species. The diverse cellular compartments each, although structurally and functionally related, actively maintain their own redox balance, which is necessary to fulfill specialized tasks. Many fundamental cellular processes such as insulin signaling, cell proliferation and differentiation and cell migration and adhesion, rely on localized changes in the redox state of signal transducers, which is mainly mediated by hydrogen peroxide (H2O2). Therefore, oxidative stress can also occur long before direct structural damage to cellular components, by disruption of the redox circuits that regulate the cellular organelles homeostasis. The hepatocyte is a systemic hub integrating the whole body metabolic demand, iron homeostasis and detoxification processes, all of which are redox-regulated processes. Imbalance of the hepatocyte’s organelles redox homeostasis underlies virtually any liver disease and is a field of intense research activity. This review recapitulates the evolving concept of oxidative stress in the diverse cellular compartments, highlighting the principle mechanisms of oxidative stress occurring in the healthy and wounded hepatocyte.

Abstract 223: S-glutathiolation Uncouples Endothelial Nitric Oxide (NO) Synthase, Switching Enzyme from NO to Superoxide Production

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Chun-An Chen ◽  
Lawrence J Druhan ◽  
Tse-Yao Wang ◽  
Yeong-Renn Chen ◽  
Jay L Zweier
Keyword(s):  
Oxidative Stress ◽  
Protein Modification ◽  
Redox Regulation ◽  
Cardiovascular Function ◽  
Heart Association ◽  
Protein S ◽  
No Production ◽  
Protein Thiols ◽  
Mixed Disulfides ◽  
Endothelial Nitric Oxide

Overproduction of superoxide (•O 2 − ) and •O 2 − -derived oxidants increases cellular oxidative stress. This can lead to cell death, via apoptosis or necrosis. An important response of protein thiols to oxidative stress is reversible formation of protein mixed disulfides via S-glutathiolation. This redox based protein modification is thought to play an important role as an adaptive response to oxidative injury in cells, or alternatively in controlling cellular signaling in a manner similar to phosphorylation. Protein S-glutathiolation is increased in the post-ischemic heart. Human eNOS, which is of critical importance in maintaining cardiovascular function, contains 29 cysteinyl residues. To investigate the effects of S-glutathiolation on the regulation of eNOS function and its relation to cardiovascular diseases, eNOS functional alterations induced by S-glutathiolation were studied. Additionally, LC/MS/MS was used to determine the precise residues of eNOS involved in this redox-dependent thiol modification. S-glutatiolation significantly reduced NO production from heNOS, with a 63% decrease induced by incubation with 2 mM GSSG in vitro . This process was reversible by addition of DTT. Alkylation of the cysteinyl residues with N-ethylmaleimide (NEM) completely inhibited NO production. S-glutathiolation of an uncoupled heNOS increased •O 2 − generation (> 70%), and this increase was only partially blocked by L-NAME, implicating the reductase site as the source for the increased •O 2 − generation. When the cysteinyl residues were all alkylated with NEM, the •O 2 − generation from eNOS was dramatically increased (+2.4-fold), and this increase was not inhibited by L-NAME. We have identified three cysteine residues, C 382 , C 689 and C 908 as sights of S-glutathiolation in heNOS, all three of which are conserved in all known mammalian eNOS enzymes. Therefore, cysteinyl residues are critical for the regulation of eNOS coupling, and S-glutatiolation of specific residues switches eNOS from an NO producing to a •O 2 − generating enzyme, by inducing electron leakage from the reductase domain. As such, S-glutathiolation provides a novel mechanism for the regulation of heNOS, defining a unique pathway for the redox regulation of cardiovascular function. This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).

Thiol-based mechanisms of the thioredoxin and glutaredoxin systems: implications for diseases in the cardiovascular system

2007 ◽  
Vol 292 (3) ◽  
pp. H1227-H1236 ◽  
Author(s):  
Carsten Berndt ◽  
Christopher Horst Lillig ◽  
Arne Holmgren
Keyword(s):  
Oxidative Stress ◽  
Mammalian Cells ◽  
Redox State ◽  
Ischemia Reperfusion ◽  
Thioredoxin Reductase ◽  
Antioxidant Systems ◽  
Cardiovascular Disorders ◽  
Active Site Cysteine ◽  
Fold Family ◽  
Protein Thiols

Reactive oxygen species (ROS) and the cellular thiol redox state are crucial mediators of multiple cell processes like growth, differentiation, and apoptosis. Excessive ROS production or oxidative stress is associated with several diseases, including cardiovascular disorders like ischemia-reperfusion. To prevent ROS-induced disorders, the heart is equipped with effective antioxidant systems. Key players in defense against oxidative stress are members of the thioredoxin-fold family of proteins. Of these, thioredoxins and glutaredoxins maintain a reduced intracellular redox state in mammalian cells by the reduction of protein thiols. The reversible oxidation of Cys-Gly-Pro-Cys or Cys-Pro(Ser)-Tyr-Cys active site cysteine residues is used in reversible electron transport. Thioredoxins and glutaredoxins belong to corresponding systems consisting of NADPH, thioredoxin reductase, and thioredoxin or NADPH, glutathione reductase, glutathione, and glutaredoxin, respectively. Thioredoxin as well as glutaredoxin activities appear to be very important for the progression and severity of several cardiovascular disorders. These proteins function not only as antioxidants, they inhibit or activate apoptotic signaling molecules like apoptosis signal-regulating kinase 1 and Ras or transcription factors like NF-κB. Thioredoxin activity is regulated by the endogenous inhibitor thioredoxin-binding protein 2 (TBP-2), indicating an important role of the balance between thioredoxin and TBP-2 levels in cardiovascular diseases. In this review, we will summarize cardioprotective effects of endogenous thioredoxin and glutaredoxin systems as well as the high potential in clinical applications of exogenously applied thioredoxin or glutaredoxin or the induction of endogenous thioredoxin and glutaredoxin systems.

scholarly journals Nucleoredoxin-Dependent Targets and Processes in Neuronal Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Claudia Urbainsky ◽  
Rolf Nölker ◽  
Marcel Imber ◽  
Adrian Lübken ◽  
Jörg Mostertz ◽  
...  
Keyword(s):  
Redox State ◽  
Redox Regulation ◽  
Neuroblastoma Cells ◽  
Neuronal Cell ◽  
Biological Processes ◽  
Quantitative Mass Spectrometry ◽  
Mixed Disulfide ◽  
Protein Thiols ◽  
Thiol Redox State ◽  
Thiol Redox

Nucleoredoxin (Nrx) is an oxidoreductase of the thioredoxin family of proteins. It was shown to act as a signal transducer in some pathways; however, so far, no comprehensive analysis of its regulated substrates and functions was available. Here, we used a combination of two different strategies to fill this gap. First, we analyzed the thiol-redox state of the proteome of SH-SY5Y neuroblastoma cells depleted of Nrx compared to control cells using a differential thiol-labeling technique and quantitative mass spectrometry. 171 proteins were identified with an altered redox state; 161 of these were more reduced in the absence of Nrx. This suggests functions of Nrx in the oxidation of protein thiols. Second, we utilized the active site mutant Cys208Ser of Nrx, which stabilizes a mixed disulfide intermediate with its substrates and therefore trapped interacting proteins from the mouse brain (identifying 1710 proteins) and neuronal cell culture extracts (identifying 609 proteins). Profiling of the affected biological processes and molecular functions in cells of neuronal origin suggests numerous functions of Nrx in the redox regulation of metabolic pathways, cellular morphology, and signal transduction. These results characterize Nrx as a cellular oxidase that itself may be oxidized by the formation of disulfide relays with peroxiredoxins.

scholarly journals How N-Acetylcysteine Supplementation Affects Redox Regulation, Especially at Mitohormesis and Sarcohormesis Level: Current Perspective

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 153
Author(s):  
Aslı Devrim-Lanpir ◽  
Lee Hill ◽  
Beat Knechtle
Keyword(s):  
Oxidative Stress ◽  
Oxidative Metabolism ◽  
Adaptive Response ◽  
Redox Regulation ◽  
Therapeutic Agent ◽  
Metabolic Effects ◽  
Metabolic Adaptations ◽  
Current Perspective ◽  
Exercise Induced ◽  
Response To Exercise

Exercise frequently alters the metabolic processes of oxidative metabolism in athletes, including exposure to extreme reactive oxygen species impairing exercise performance. Therefore, both researchers and athletes have been consistently investigating the possible strategies to improve metabolic adaptations to exercise-induced oxidative stress. N-acetylcysteine (NAC) has been applied as a therapeutic agent in treating many diseases in humans due to its precursory role in the production of hepatic glutathione, a natural antioxidant. Several studies have investigated NAC’s possible therapeutic role in oxidative metabolism and adaptive response to exercise in the athletic population. However, still conflicting questions regarding NAC supplementation need to be clarified. This narrative review aims to re-evaluate the metabolic effects of NAC on exercise-induced oxidative stress and adaptive response developed by athletes against the exercise, especially mitohormetic and sarcohormetic response.

scholarly journals Imaging NAD(H) Redox Alterations in Cryopreserved Alveolar Macrophages from Ozone-Exposed Mice and the Impact of Nutrient Starvation during Long Lag Times

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 767
Author(s):  
He N. Xu ◽  
Joanna Floros ◽  
Lin Z. Li ◽  
Shaili Amatya
Keyword(s):  
Oxidative Stress ◽  
Alveolar Macrophages ◽  
Redox State ◽  
Redox Status ◽  
Nutrient Starvation ◽  
Ozone Exposure ◽  
Reduced Form ◽  
Time Period ◽  
Lag Times ◽  
The Impact

Employing the optical redox imaging technique, we previously identified a significant redox shift of nicotinamide adenine dinucleotide (NAD and the reduced form NADH) in freshly isolated alveolar macrophages (AM) from ozone-exposed mice. The goal here was twofold: (a) to determine the NAD(H) redox shift in cryopreserved AM isolated from ozone-exposed mice and (b) to investigate whether there is a difference in the redox status between cryopreserved and freshly isolated AM. We found: (i) AM from ozone-exposed mice were in a more oxidized redox state compared to that from filtered air (FA)-exposed mice, consistent with the results obtained from freshly isolated mouse AM; (ii) under FA exposure, there was no significant NAD(H) redox difference between fresh AM that had been placed on ice for 2.5 h and cryopreserved AM; however, under ozone exposure, fresh AM were more oxidized than cryopreserved AM; (iii) via the use of nutrient starvation and replenishment and H2O2-induced oxidative stress of an AM cell line, we showed that this redox difference between cryopreserved and freshly isolated AM is likely the result of the double “hit”, i.e., the ozone-induced oxidative stress plus nutrient starvation that prevented freshly isolated AM from a full recovery after being on ice for a prolonged time period. The cryopreservation technique we developed eliminates/minimizes the effects of oxidative stress and nutrient starvation on cells. This method can be adopted to preserve lung macrophages from animal models or clinical patients for further investigations.

scholarly journals Serum Albumin Redox States: More than Oxidative Stress Biomarker

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 503
Author(s):  
Fuka Tabata ◽  
Yasuaki Wada ◽  
Satomi Kawakami ◽  
Kazuhiro Miyaji
Keyword(s):  
Oxidative Stress ◽  
Serum Albumin ◽  
Animal Studies ◽  
Redox State ◽  
Ex Vivo ◽  
Pathological Condition ◽  
Analytical Techniques ◽  
Cysteine Residue ◽  
Research Field ◽  
Systemic Oxidative Stress

Serum albumin is the most abundant circulating protein in mammals including humans. It has three isoforms according to the redox state of the free cysteine residue at position 34, named as mercaptalbumin (reduced albumin), non-mercaptalbumin-1 and -2 (oxidized albumin), respectively. The serum albumin redox state has long been viewed as a biomarker of systemic oxidative stress, as the redox state shifts to a more oxidized state in response to the severity of the pathological condition in various diseases such as liver diseases and renal failures. However, recent ex vivo studies revealed oxidized albumin per se could aggravate the pathological conditions. Furthermore, the possibility of the serum albumin redox state as a sensitive protein nutrition biomarker has also been demonstrated in a series of animal studies. A paradigm shift is thus ongoing in the research field of the serum albumin. This article provides an updated overview of analytical techniques for serum albumin redox state and its association with human health, focusing on recent findings.

A manganese oxide nanozyme prevents the oxidative damage of biomolecules without affecting the endogenous antioxidant system

Nanoscale ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 3855-3863 ◽  
Author(s):  
Namrata Singh ◽  
Mohammed Azharuddin Savanur ◽  
Shubhi Srivastava ◽  
Patrick D'Silva ◽  
Govindasamy Mugesh
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Manganese Oxide ◽  
Antioxidant System ◽  
Mammalian Cells ◽  
Redox State ◽  
Stress Conditions ◽  
System P ◽  
Endogenous Antioxidant ◽  
Antioxidant Machinery

Multi-enzyme mimetic Mn3O4 nanoflowers (Mp) modulate the redox state of mammalian cells without altering the cellular antioxidant machinery under oxidative stress conditions.

scholarly journals Reactive Oxygen Species-Mediated Control of Mitochondrial Biogenesis

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Edgar D. Yoboue ◽  
Anne Devin
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Biogenesis ◽  
Redox State ◽  
Mitochondrial Genomes ◽  
Oxygen Species ◽  
Mitochondrial Content ◽  
Cellular Redox ◽  
High Importance ◽  
Complex Process ◽  
Long Time

Mitochondrial biogenesis is a complex process. It necessitates the contribution of both the nuclear and the mitochondrial genomes and therefore crosstalk between the nucleus and mitochondria. It is now well established that cellular mitochondrial content can vary according to a number of stimuli and physiological states in eukaryotes. The knowledge of the actors and signals regulating the mitochondrial biogenesis is thus of high importance. The cellular redox state has been considered for a long time as a key element in the regulation of various processes. In this paper, we report the involvement of the oxidative stress in the regulation of some actors of mitochondrial biogenesis.

Carvedilol protects against cisplatin-induced oxidative stress, redox state unbalance and apoptosis in rat kidney mitochondria

2011 ◽  
Vol 189 (1-2) ◽  
pp. 45-51 ◽  
Author(s):  
M.A. Carvalho Rodrigues ◽  
J.L. Rodrigues ◽  
N.M. Martins ◽  
F. Barbosa ◽  
C. Curti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Redox State ◽  
Rat Kidney ◽  
Kidney Mitochondria
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