scholarly journals Resilience to oxidative and nitrosative stress is mediated by the stressosome, RsbP and SigB inBacillus subtilis.

2018 ◽  
Author(s):  
Vina Tran ◽  
Kara Geraci ◽  
Giovanni Midili ◽  
William Satterwhite ◽  
Rachel Wright ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Environmental Stress ◽  
Nitrosative Stress ◽  
Nutritional Stress ◽  
Cross Protection ◽  
Cross Resistance ◽  
Oxidative And Nitrosative Stress ◽  
General Stress Response ◽  
Energy Stress ◽  
Highly Sensitive

AbstractA bacterium’s ability to thrive in the presence of multiple environmental stressors simultaneously determines its resilience. We showed that activation of the SigB-controlled general stress response by mild environmental or nutritional stress provided significant cross-protection to subsequent lethal oxidative, disulfide and nitrosative stress exposure. SigB activation is mediated via the stressosome and RsbP, the main conduits of environmental and nutritional stress, respectively. Cells exposed to mild environmental stress while lacking the major stressosome components RsbT or RsbRA were highly sensitive to subsequent oxidative stress, whereasrsbRB, rsbRC, rsbRDandytvAnull mutants showed a spectrum of sensitivity, confirming their redundant roles and suggesting they could modulate the signal generated by environmental stress or oxidative stress. Furthermore, from mutant analysis we infer that RsbRA phosphorylation by RsbT was important for this cross-resistance to oxidative stress. By contrast, cells encountering stationary phase stress required RsbP but not RsbT to survive subsequent oxidative stress caused by hydrogen peroxide and diamide. Interestingly, optimum cross-protection against nitrosative stress caused by SNP required SigB but not the known regulators, RsbT and RsbP, suggesting an additional and as yet uncharacterized route of SigB activation independent of the known environmental and energy-stress pathways. Together, these results provide a mechanism for howBacillus subtilispromotes enhanced resistance against lethal oxidative stress during likely physiologically relevant conditions such as mild environmental or nutrient stress.

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.

scholarly journals Co-Exposure of Cardiomyocytes to IFN-γ and TNF-α Induces Mitochondrial Dysfunction and Nitro-Oxidative Stress: Implications for the Pathogenesis of Chronic Chagas Disease Cardiomyopathy

2021 ◽  
Vol 12 ◽  
Author(s):  
João Paulo Silva Nunes ◽  
Pauline Andrieux ◽  
Pauline Brochet ◽  
Rafael Ribeiro Almeida ◽  
Eduardo Kitano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acid ◽  
Mitochondrial Dysfunction ◽  
Chagas Disease ◽  
Nitrosative Stress ◽  
Acid Oxidation ◽  
Oxidative And Nitrosative Stress ◽  
Human Cardiomyocytes ◽  
Tnf Α ◽  
Ifn Γ

Infection by the protozoan Trypanosoma cruzi causes Chagas disease cardiomyopathy (CCC) and can lead to arrhythmia, heart failure and death. Chagas disease affects 8 million people worldwide, and chronic production of the cytokines IFN-γ and TNF-α by T cells together with mitochondrial dysfunction are important players for the poor prognosis of the disease. Mitochondria occupy 40% of the cardiomyocytes volume and produce 95% of cellular ATP that sustain the life-long cycles of heart contraction. As IFN-γ and TNF-α have been described to affect mitochondrial function, we hypothesized that IFN-γ and TNF-α are involved in the myocardial mitochondrial dysfunction observed in CCC patients. In this study, we quantified markers of mitochondrial dysfunction and nitro-oxidative stress in CCC heart tissue and in IFN-γ/TNF-α-stimulated AC-16 human cardiomyocytes. We found that CCC myocardium displayed increased levels of nitro-oxidative stress and reduced mitochondrial DNA as compared with myocardial tissue from patients with dilated cardiomyopathy (DCM). IFN-γ/TNF-α treatment of AC-16 cardiomyocytes induced increased nitro-oxidative stress and decreased the mitochondrial membrane potential (ΔΨm). We found that the STAT1/NF-κB/NOS2 axis is involved in the IFN-γ/TNF-α-induced decrease of ΔΨm in AC-16 cardiomyocytes. Furthermore, treatment with mitochondria-sparing agonists of AMPK, NRF2 and SIRT1 rescues ΔΨm in IFN-γ/TNF-α-stimulated cells. Proteomic and gene expression analyses revealed that IFN-γ/TNF-α-treated cells corroborate mitochondrial dysfunction, transmembrane potential of mitochondria, altered fatty acid metabolism and cardiac necrosis/cell death. Functional assays conducted on Seahorse respirometer showed that cytokine-stimulated cells display decreased glycolytic and mitochondrial ATP production, dependency of fatty acid oxidation as well as increased proton leak and non-mitochondrial oxygen consumption. Together, our results suggest that IFN-γ and TNF-α cause direct damage to cardiomyocytes’ mitochondria by promoting oxidative and nitrosative stress and impairing energy production pathways. We hypothesize that treatment with agonists of AMPK, NRF2 and SIRT1 might be an approach to ameliorate the progression of Chagas disease cardiomyopathy.

scholarly journals The Changes of Expression and Methylation of Genes Involved in Oxidative Stress in Course of Chronic Mild Stress and Antidepressant Therapy with Agomelatine

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 644
Author(s):  
Paulina Wigner ◽  
Ewelina Synowiec ◽  
Paweł Jóźwiak ◽  
Piotr Czarny ◽  
Michał Bijak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitrosative Stress ◽  
Mononuclear Cells ◽  
Methylation Status ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Oxidative And Nitrosative Stress ◽  
Peripheral Blood Mononuclear ◽  
Taqman Gene Expression Assay ◽  
The Brain

Preclinical studies conducted so far suggest that oxidative stress processes may be associated with the mechanism of depression development. This study shows the effects of chronic administration of agomelatine on expression and the methylation status of Sod1, Sod2, Gpx1, Gpx4, Cat, Nos1, and Nos2 in the brain stricture and blood in the chronic mild stress (CMS) animal model of depression. The animals were exposed to the CMS procedure and treatment with agomelatine (10 mg/kg/day, IP) for five weeks and then were sacrificed. TaqMan Gene Expression Assay, Western blot, and methylation-sensitive high-resolution melting techniques were used to evaluate mRNA and protein expression of the genes, and the methylation status of their promoters. Gpx1, Gpx4, and Sod2 expression in the PBMCs and Sod1 and Sod2 expression in the brain were reduced in the stressed group after agomelatine administration. CMS caused an increase in the methylation of the third Gpx4 promoter in peripheral blood mononuclear cells and Gpx1 promoter in the cerebral cortex. Additionally, stressed rats treated with agomelatine displayed a significantly lower Gpx4 level in the hypothalamus. The results confirm the hypothesis that the CMS procedure and agomelatine administration change the expression level and methylation status of the promoter region of genes involved in oxidative and nitrosative stress.

scholarly journals Oxidative-Nitrosative Stress and Myocardial Dysfunctions in Sepsis: Evidence from the Literature and Postmortem Observations

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
M. Neri ◽  
I. Riezzo ◽  
C. Pomara ◽  
S. Schiavone ◽  
E. Turillazzi
Keyword(s):  
Oxidative Stress ◽  
Current Literature ◽  
Cardiac Dysfunction ◽  
Nitrosative Stress ◽  
Myocardial Dysfunction ◽  
Critical Role ◽  
Therapeutic Effects ◽  
Oxidative And Nitrosative Stress ◽  
Antioxidant Agents

Background. Myocardial depression in sepsis is common, and it is associated with higher mortality. In recent years, the hypothesis that the myocardial dysfunction during sepsis could be mediated by ischemia related to decreased coronary blood flow waned and a complex mechanism was invoked to explain cardiac dysfunction in sepsis. Oxidative stress unbalance is thought to play a critical role in the pathogenesis of cardiac impairment in septic patients.Aim. In this paper, we review the current literature regarding the pathophysiology of cardiac dysfunction in sepsis, focusing on the possible role of oxidative-nitrosative stress unbalance and mitochondria dysfunction. We discuss these mechanisms within the broad scenario of cardiac involvement in sepsis.Conclusions. Findings from the current literature broaden our understanding of the role of oxidative and nitrosative stress unbalance in the pathophysiology of cardiac dysfunction in sepsis, thus contributing to the establishment of a relationship between these settings and the occurrence of oxidative stress. The complex pathogenesis of septic cardiac failure may explain why, despite the therapeutic strategies, sepsis remains a big clinical challenge for effectively managing the disease to minimize mortality, leading to consideration of the potential therapeutic effects of antioxidant agents.

Micro Composite Palmitoylethanolamide/Rutin Reduces Vascular Injury through Modulation of the Nrf2/HO−1 and NF-kB Pathways

2021 ◽  
Vol 28 ◽  
Author(s):  
Roberta Fusco ◽  
Rosalba Siracusa ◽  
Enrico Gugliandolo ◽  
Alessio Filippo Peritore ◽  
Ramona D’Amico ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Adhesion Molecules ◽  
Vascular Injury ◽  
Nitrosative Stress ◽  
Neointimal Hyperplasia ◽  
Vascular Damage ◽  
Oxidative And Nitrosative Stress ◽  
Monocyte Chemoattractant Protein 1 ◽  
Vessel Morphology ◽  
And Oxidative Stress

Background: Vascular remodeling processes induced by acute and chronic injuries are characterized by inflammation and oxidative stress. In arteriosclerosis, atherosclerosis and restenosis, the progression of neointimal hyperplasia is a key event of vascular damage. Objective: Our study was aimed to investigate the inflammation and oxidative stress development during vascular impairment and the potential efficacy of treatment of new micro composite N-palmitoylethanolamine /Rutin at a ratio of 1:1 (PEA/RUT). The anti-inflammatory effects of Palmitoylethanolamide (PEA) are well known. Rutin has important pharmacological actions, including antioxidant and vasoprotective. Methods: As model of vascular injury we used the complete ligature of the left carotid artery for fourteen days and administered PEA/RUT at the dose of 10 mg/Kg. Results: This study demonstrated that after fourteen days carotid ligation there is a substantial structural change in the vessel morphology, with inflammatory cells infiltration and reactive oxygen species production. PEA/RUT administration reduced change in vascular morphology, cytokines like monocyte chemoattractant protein-1 (MCP-1) and adhesion molecules expression like intercellular adhesion molecules-1 (ICAM-1), proinflammatory cytokines production (IL-1, IL-6 and TNF-), oxidative and nitrosative stress (nitrotyrosine and PARP expression and NRF2 pathway). Conclusions: Our data clearly demonstrate the beneficial effect of PEA/RUT administration in reducing inflammation, oxidative stress and vascular damage.

ROLE OF PREGNAN-X-RECEPTOR IN CELL RESISTANCE TO NITROSATIVE AND OXIDATIVE STRESS

2021 ◽  
Author(s):  
Yulia Abalenikhina ◽  
◽  
Elena A. Sudakova ◽  
Pelageya Erokhina ◽  
Aleksey Shchulkin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Viability ◽  
Nitrosative Stress ◽  
Pregnane X Receptor ◽  
Cell Resistance ◽  
Oxidative And Nitrosative Stress ◽  
High Concentrations ◽  
And Oxidative Stress

The article discusses the new role of pregnane X receptor (PXR) under conditions of oxidative and nitrosative stress. The results showed that the effect of hydrogen peroxide and S-nitrosoglu-tathione in high concentrations on Caco-2 cells leads to a decrease in cell viability, which is accompanied by an increase in the amount of PXR. These changes are offset by the addition of ketoconazole (inhibitor of PXR) to the medium.

scholarly journals PREVENTIVE ROLES OF BIOACTIVE NATURAL COMPOUNDS IN OXIDATIVE AND NITROSATIVE STRESS MEDIATED PATHOPHYSIOLOGY OF DIABETES MELLITUS

2019 ◽  
pp. 34-43
Author(s):  
SATYAPRAKASH BERAIYA ◽  
PIR MOHAMMAD ISHFAQ ◽  
ZAVED AHMAD ◽  
SWATI TRIPATHI ◽  
SIDDHARTHA KUMAR MISHRA
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Bioactive Compounds ◽  
Fruits And Vegetables ◽  
Nitrosative Stress ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Fundamental Aspect ◽  
Oxidative And Nitrosative Stress ◽  
Prevention Of Diabetes

Oxidative stress has emerged as one of the targets in several medical conditions and in several types of clinical researches. Growing evidences from research on diverse diseases show that oxidative stress is conjoined with the pathogenesis of diabetes and its complications. This review has examined the role of oxidative stress in the pathogenesis of insulin resistance and beta-cell dysfunction. A vast variety of medicinal plants and products have been utilized for the prevention of diabetes and its related complications. Natural products such as phenolic acids and flavonoids construct one of the most ubiquitous groups of plant phenolics. At present, the effect of dietary phenolics is of extreme concern due to their antioxidant, free radical scavenging, and as quenchers of singlet oxygen formation. Reactive oxygen species (ROS) as well as reactive nitrogen species play either harmful or beneficial roles in biological systems depending on pathophysiological conditions. This review extends on the fundamental aspect of ROS in biological processes and diseases and how natural bioactive compounds of fruits and vegetables regulate their health improving properties. Flavonoids and phenolics acids are the most important groups of secondary metabolites and bioactive compounds in plants. Diverse phytochemical agents have become the backbone in pharmacotherapy of diabetes by virtue of their antioxidant properties along with their other pharmacological actions. Consequently, accession to obstruction the generation of reactive free radicals or abduct the reactive free radical may yield direct and casual approach for the medication of diabetes and its complications.

scholarly journals Renoprotection of Selected Antioxidant-Rich Foods (Water Spinach and Red Grape) and Probiotics in Gentamicin-Induced Nephrotoxicity and Oxidative Stress in Rats

Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 60
Author(s):  
Sneha Sarwar ◽  
Md. Jamal Hossain ◽  
Nafis Md. Irfan ◽  
Tamima Ahsan ◽  
Md. Saidul Arefin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Serum Creatinine ◽  
Nitrosative Stress ◽  
Female Rats ◽  
Uremic Toxin ◽  
Water Spinach ◽  
Oxidative And Nitrosative Stress ◽  
Red Grape ◽  
And Oxidative Stress

Objectives: The current study investigated the curative effects of two selected antioxidant-rich foods (water spinach and red grape) and probiotics on the kidney exposed to nephrotoxicity induced by gentamicin. Methods: A total of 30 Wistar Albino female rats equally divided into six groups were studied for seven days. Except for the normal control (NC) group, all groups received 80 mg/kg/day gentamicin (GEN) injection intra-peritoneally for seven days. NC and GEN groups received only regular diet. In the water spinach group (GEN + WS) and red grape (GEN + RG) groups, rats were provided with 20 g/rat/day of boiled water spinach and 5 mL/rat/day of red grape juice, respectively. The probiotic (GEN + P4) and (GEN + P8) groups received 4 × 109 and 8 × 109 viable bacteria, respectively. On the 8th day, all the rats were sacrificed to collect blood and kidney. Serum creatinine, urea, uric acid, malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) were analyzed. In addition, kidney histopathology was taken for final observation. Results: Both antioxidant-rich foods and probiotic (P4) significantly (p < 0.05) attenuated the GEN-induced oxidative and nitrosative stress and improved kidney function by lowering uremic toxin (serum creatinine, and uric acid) levels. Histopathological findings of kidney tissues of all groups were consistent with the biochemical findings. Conclusion: The current preclinical study suggests that the consumption of antioxidant-rich foods might be a promising fighting option against gentamycin-induced nephrotoxicity and oxidative stress. However, extensive studies and clinical monitoring are immediately required to determine the appropriate probiotic doses and mechanism of action for such effects.

scholarly journals Isocitrate Dehydrogenase Is Important for Nitrosative Stress Resistance in Cryptococcus neoformans, but Oxidative Stress Resistance Is Not Dependent on Glucose-6-Phosphate Dehydrogenase

2010 ◽  
Vol 9 (6) ◽  
pp. 971-980 ◽  
Author(s):  
Sarah M. Brown ◽  
Rajendra Upadhya ◽  
James D. Shoemaker ◽  
Jennifer K. Lodge
Keyword(s):  
Oxidative Stress ◽  
Cryptococcus Neoformans ◽  
Stress Resistance ◽  
Isocitrate Dehydrogenase ◽  
Nitrosative Stress ◽  
Stress Sensitivity ◽  
Wild Type ◽  
Oxidative And Nitrosative Stress ◽  
Content Type ◽  
Glucose 6 Phosphate Dehydrogenase

ABSTRACT The opportunistic intracellular fungal pathogen Cryptococcus neoformans depends on many antioxidant and denitrosylating proteins and pathways for virulence in the immunocompromised host. These include the glutathione and thioredoxin pathways, thiol peroxidase, cytochrome c peroxidase, and flavohemoglobin denitrosylase. All of these ultimately depend on NADPH for either catalytic activity or maintenance of a reduced, functional form. The need for NADPH during oxidative stress is well established in many systems, but a role in resistance to nitrosative stress has not been as well characterized. In this study we investigated the roles of two sources of NADPH, glucose-6-phosphate dehydrogenase (Zwf1) and NADP+-dependent isocitrate dehydrogenase (Idp1), in production of NADPH and resistance to oxidative and nitrosative stress. Deletion of ZWF1 in C. neoformans did not result in an oxidative stress sensitivity phenotype or changes in the amount of NADPH produced during oxidative stress compared to those for the wild type. Deletion of IDP1 resulted in greater sensitivity to nitrosative stress than to oxidative stress. The amount of NADPH increased 2-fold over that in the wild type during nitrosative stress, and yet the idp1Δ strain accumulated more mitochondrial damage than the wild type during nitrosative stress. This is the first report of the importance of Idp1 and NADPH for nitrosative stress resistance.

scholarly journals Upregulation of Cysteine Synthase and Cystathionine β-Synthase Contributes to Leishmania braziliensis Survival under Oxidative Stress

2015 ◽  
Vol 59 (8) ◽  
pp. 4770-4781 ◽  
Author(s):  
Ibeth Romero ◽  
Jair Téllez ◽  
Alvaro José Romanha ◽  
Mario Steindel ◽  
Edmundo Carlos Grisard
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Nitrosative Stress ◽  
De Novo ◽  
Stress Conditions ◽  
Leishmania Braziliensis ◽  
Oxidative And Nitrosative Stress ◽  
Cysteine Synthase ◽  
Content Type

ABSTRACTCysteine metabolism is considered essential for the crucial maintenance of a reducing environment in trypanosomatids due to its importance as a precursor of trypanothione biosynthesis. Expression, activity, functional rescue, and overexpression of cysteine synthase (CS) and cystathionine β-synthase (CβS) were evaluated inLeishmania braziliensispromastigotes and intracellular amastigotes underin vitrostress conditions induced by hydrogen peroxide (H2O2),S-nitroso-N-acetylpenicillamine, or antimonial compounds. Our results demonstrate a stage-specific increase in the levels of protein expression and activity ofL. braziliensisCS (LbrCS) andL. braziliensisCβS (LbrCβS), resulting in an increment of total thiol levels in response to both oxidative and nitrosative stress. The rescue of the CS activity inTrypanosoma rangeli, a trypanosome that does not perform cysteine biosynthesisde novo, resulted in increased rates of survival of epimastigotes expressing the LbrCS under stress conditions compared to those of wild-type parasites. We also found that the ability ofL. braziliensispromastigotes and amastigotes overexpressing LbrCS and LbrCβS to resist oxidative stress was significantly enhanced compared to that of nontransfected cells, resulting in a phenotype far more resistant to treatment with the pentavalent form of Sbin vitro. In conclusion, the upregulation of protein expression and increment of the levels of LbrCS and LbrCβS activity alter parasite resistance to antimonials and may influence the efficacy of antimony treatment of New World leishmaniasis.

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