scholarly journals Redox Active Thiol Sensors of Oxidative and Nitrosative Stress

2012 ◽  
Vol 17 (9) ◽  
pp. 1201-1214 ◽  
Author(s):  
Andrés Vázquez-Torres
Keyword(s):  
Nitrosative Stress ◽  
Oxidative And Nitrosative Stress ◽  
Redox Active

scholarly journals Redox-Active Sensing by Bacterial DksA Transcription Factors Is Determined by Cysteine and Zinc Content

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Matthew A. Crawford ◽  
Timothy Tapscott ◽  
Liam F. Fitzsimmons ◽  
Lin Liu ◽  
Aníbal M. Reyes ◽  
...  
Keyword(s):  
Nitrosative Stress ◽  
Zinc Content ◽  
Bacterial Pathogenesis ◽  
Reactive Species ◽  
Sensory Function ◽  
Metabolic Adaptation ◽  
Oxidative And Nitrosative Stress ◽  
Nutritional Limitation ◽  
Redox Active ◽  
Sense And Respond

ABSTRACT The four-cysteine zinc finger motif of the bacterial RNA polymerase regulator DksA is essential for protein structure, canonical control of the stringent response to nutritional limitation, and thiol-based sensing of oxidative and nitrosative stress. This interdependent relationship has limited our understanding of DksA-mediated functions in bacterial pathogenesis. Here, we have addressed this challenge by complementing Δ dksA Salmonella with Pseudomonas aeruginosa dksA paralogues that encode proteins differing in cysteine and zinc content. We find that four-cysteine, zinc-bound (C4) and two-cysteine, zinc-free (C2) DksA proteins are able to mediate appropriate stringent control in Salmonella and that thiol-based sensing of reactive species is conserved among C2 and C4 orthologues. However, variations in cysteine and zinc content determine the threshold at which individual DksA proteins sense and respond to reactive species. In particular, zinc acts as an antioxidant, dampening cysteine reactivity and raising the threshold of posttranslational thiol modification with reactive species. Consequently, C2 DksA triggers transcriptional responses in Salmonella at levels of oxidative or nitrosative stress normally tolerated by Salmonella expressing C4 orthologues. Inappropriate transcriptional regulation by C2 DksA increases the susceptibility of Salmonella to the antimicrobial effects of hydrogen peroxide and nitric oxide, and attenuates virulence in macrophages and mice. Our findings suggest that the redox-active sensory function of DksA proteins is finely tuned to optimize bacterial fitness according to the levels of oxidative and nitrosative stress encountered by bacterial species in their natural and host environments. IMPORTANCE In order to cause disease, pathogenic bacteria must rapidly sense and respond to antimicrobial pressures encountered within the host. Prominent among these stresses, and of particular relevance to intracellular pathogens such as Salmonella , are nutritional restriction and the enzymatic generation of reactive oxygen and nitrogen species. The conserved transcriptional regulator DksA controls adaptive responses to nutritional limitation, as well as to oxidative and nitrosative stress. Here, we demonstrate that each of these functions contributes to bacterial pathogenesis. Our observations highlight the importance of metabolic adaptation in bacterial pathogenesis and show the mechanism by which DksA orthologues are optimized to sense the levels of oxidative and nitrosative stress encountered in their natural habitats. An improved understanding of the conserved processes used by bacteria to sense, respond to, and limit host defense will inform the development of novel strategies to treat infections caused by pathogenic, potentially multidrug-resistant bacteria.

scholarly journals Centaurium erythraea extract reduces redox imbalance and improves insulin expression and secretion in pancreatic β-cells exposed to oxidative and nitrosative stress

2020 ◽  
Vol 72 (1) ◽  
pp. 117-128
Author(s):  
Milos Djordjevic ◽  
Nevena Grdovic ◽  
Mirjana Mihailovic ◽  
Jelena Arambasic-Jovanovic ◽  
Aleksandra Uskokovic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitrosative Stress ◽  
Cell Damage ◽  
Redox Homeostasis ◽  
Protein S ◽  
Oxidative And Nitrosative Stress ◽  
Protein Levels ◽  
Insulin Expression ◽  
Redox Active ◽  
Centaurium Erythraea

Oxidative stress is one of the major mechanisms that underlies the damage of pancreatic ?-cells and defects in insulin secretion in diabetes. As herbal preparations can alleviate oxidative stress through their redox-active secondary metabolites, in this study we investigated the cytoprotective effects of Centaurium erythraea extract (CEe) against H2O2- and SNP-induced oxidative/nitrosative stress in Rin-5F ?-cells. The antioxidant activity of CEe and its effect on cell survival and insulin expression/secretion were evaluated. The CEe increased cell viability and ameliorated the disturbance of redox homeostasis in H2O2- and SNP-treated cells by decreasing DNA damage, lipid peroxidation and protein S-glutathionylation. The CEe restored GSH homeostasis in H2O2-treated ?-cells and attenuated the SNP-induced disturbance of the GSH/ GSSG ratio. The H2O2- and SNP-induced disruption of CAT, GPx, GR, MnSOD and CuZnSOD activities was adjusted by the CEe towards control values, as well as mRNA and protein levels of GPx, MnSOD and CAT. The CEe increased insulin expression/secretion particularly in H2O2-treated ?-cells, which was in accordance with the more pronounced antioxidant effect of the CEe observed in H2O2-treated ?-cells as compared to SNP-treated cells. These findings support the beneficial effect of the CEe in preventing or slowing down ?-cell damage and dysfunction caused by oxidative/nitrosative stress during diabetes development.

scholarly journals Myeloperoxidase-Related Chlorination Activity Is Positively Associated with Circulating Ceruloplasmin in Chronic Heart Failure Patients: Relationship with Neurohormonal, Inflammatory, and Nutritional Parameters

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Aderville Cabassi ◽  
Simone Maurizio Binno ◽  
Stefano Tedeschi ◽  
Gallia Graiani ◽  
Cinzia Galizia ◽  
...  
Keyword(s):  
Heart Failure ◽  
Nitrosative Stress ◽  
Defense Mechanism ◽  
Nyha Class ◽  
Protein Nitration ◽  
Class Iii ◽  
Oxidative And Nitrosative Stress ◽  
Radical Production ◽  
Antioxidant Function ◽  
The Relationship

Rationale. Heart failure (HF) is accompanied by the development of an imbalance between oxygen- and nitric oxide-derived free radical production leading to protein nitration. Both chlorinating and peroxidase cycle of Myeloperoxidase (MPO) contribute to oxidative and nitrosative stress and are involved in tyrosine nitration of protein. Ceruloplasmin (Cp) has antioxidant function through its ferroxidase I (FeOxI) activity and has recently been proposed as a physiological defense mechanism against MPO inappropriate actions.Objective. We investigated the relationship between plasma MPO-related chlorinating activity, Cp and FeOxI, and nitrosative stress, inflammatory, neurohormonal, and nutritional biomarkers in HF patients.Methods and Results. In chronic HF patients (n=81, 76±9 years, NYHA Class II (26); Class III (29); Class IV (26)) and age-matched controls (n=17, 75±11 years, CTR), plasma MPO chlorinating activity, Cp, FeOxI, nitrated protein, free Malondialdehyde, BNP, norepinephrine, hsCRP, albumin, and prealbumin were measured. Plasma MPO chlorinating activity, Cp, BNP, norepinephrine, and hsCRP were increased in HF versus CTR. FeOxI, albumin, and prealbumin were decreased in HF. MPO-related chlorinating activity was positively related to Cp (r= 0.363,P<0.001), nitrated protein, hsCRP, and BNP and inversely to albumin.Conclusions. Plasma MPO chlorinated activity is increased in elderly chronic HF patients and positively associated with Cp, inflammatory, neurohormonal, and nitrosative parameters suggesting a role in HF progression.

scholarly journals Methane and Inflammation - A Review (Fight Fire with Fire)

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Marietta Zita Poles ◽  
László Juhász ◽  
Mihály Boros
Keyword(s):  
Stress Responses ◽  
Nitrosative Stress ◽  
Ischemia Reperfusion ◽  
Signalling Pathways ◽  
Experimental Conditions ◽  
Neuroprotective Effects ◽  
Oxidative And Nitrosative Stress ◽  
Carbohydrate Fermentation ◽  
Insight Into

AbstractMammalian methanogenesis is regarded as an indicator of carbohydrate fermentation by anaerobic gastrointestinal flora. Once generated by microbes or released by a non-bacterial process, methane is generally considered to be biologically inactive. However, recent studies have provided evidence for methane bioactivity in various in vivo settings. The administration of methane either in gas form or solutions has been shown to have anti-inflammatory and neuroprotective effects in an array of experimental conditions, such as ischemia/reperfusion, endotoxemia and sepsis. It has also been demonstrated that exogenous methane influences the key regulatory mechanisms and cellular signalling pathways involved in oxidative and nitrosative stress responses. This review offers an insight into the latest findings on the multi-faceted organ protective activity of exogenous methane treatments with special emphasis on its versatile effects demonstrated in sepsis models.

scholarly journals The role of oxidative and nitrosative stress in the pathology of osteoarthritis: Novel candidate biomarkers for quantification of degenerative changes in the knee joint

2018 ◽  
Vol 10 (2) ◽  
Author(s):  
Alexander Franz ◽  
Laura Joseph ◽  
Constantin Mayer ◽  
Jan-Frieder Harmsen ◽  
Holger Schrumpf ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Synovial Fluid ◽  
Knee Joint ◽  
Human Serum ◽  
Synovial Membrane ◽  
Nitrosative Stress ◽  
Control Groups ◽  
Oxidative And Nitrosative Stress ◽  
And Oxidative Stress

Osteoarthritis (OA) is the most frequently diagnosed joint disorder worldwide with increasing prevalence and crucial impact on the quality of life of affected patients through chronic pain, decreasing mobility and invalidity. Although some risk factors, such as age, obesity and previous joint injury are well established, the exact pathogenesis of OA on a cellular and molecular level remains less understood. Today, the role of nitrosative and oxidative stress has not been investigated conclusively in the pathogenesis of OA yet. Therefore, the objective of this study was to identify biological substances for oxidative and nitrosative stress, which mirror the degenerative processes in an osteoarthritic joint. 69 patients suffering from a diagnosed knee pain participated in this study. Based on the orthopedic diagnosis, patients were classified into an osteoarthritis group (OAG, n=24) or in one of two control groups (meniscopathy, CG1, n=11; anterior cruciate ligament rupture, CG2, n=34). Independently from the study protocol, all patients underwent an invasive surgical intervention which was used to collect samples from the synovial membrane, synovial fluid and human serum. Synovial biopsies were analyzed histopathologically for synovitis (Krenn-Score) and immunohistochemically for detection of end products of oxidative (8-isoprostane F2α) and nitrosative (3-nitrotyrosine) stress. Additionally, the fluid samples were analyzed for 8-isoprostane F2α and 3-nitrotyrosine by competitive ELISA method. The analyzation of inflammation in synovial biopsies revealed a slight synovitis in all three investigated groups. Detectable concentrations of 3-nitrotyrosine were reported in all three investigated groups without showing any significant differences between the synovial biopsies, fluid or human serum. In contrast, significant increased concentrations of 8-isoprostane F2α were detected in OAG compared to both control groups. Furthermore, our data showed a significant correlation between the histopathological synovitis and oxidative stress in OAG (r=0.728, P<0.01). There were no significant differences between the concentrations of 8-isoprostane F2α in synovial fluid and human serum. The findings of the current study support the hypothesis that oxidative and nitrosative stress are components of the multi-factory pathophysiological formation of OA. It seems reasonable that an inflammatory process in the synovial membrane triggers the generation of oxidative and nitrosative acting substances which can lead to a further degradation of the articular cartilage. Based on correlations between the observed degree of inflammation and investigated biomarkers, especially 8-isoprostane F2α seems to be a novel candidate biomarker for OA. However, due to the finding that also both control groups showed increased concentrations of selected biomarkers, future studies have to validate the diagnostic potential of these biomarkers in OA and in related conditions of the knee joint.

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