scholarly journals MsrR is a thiol-based oxidation-sensing regulator of the XRE family that modulates C. glutamicum oxidative stress resistance

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Meiru Si ◽  
Can Chen ◽  
Jingyi Zhong ◽  
Xiaona Li ◽  
Yang Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Resistance ◽  
Critical Role ◽  
Extreme Environment ◽  
Growth Conditions ◽  
Antioxidant Genes ◽  
Stress Genes ◽  
Elevated Expression ◽  
Mercaptopyruvate Sulfurtransferase ◽  
Xenobiotic Response

Abstract Background Corynebacterium glutamicum thrives under oxidative stress caused by the inevitably extreme environment during fermentation as it harbors antioxidative stress genes. Antioxidant genes are controlled by pathway-specific sensors that act in response to growth conditions. Although many families of oxidation-sensing regulators in C. glutamicum have been well described, members of the xenobiotic-response element (XRE) family, involved in oxidative stress, remain elusive. Results In this study, we report a novel redox-sensitive member of the XER family, MsrR (multiple stress resistance regulator). MsrR is encoded as part of the msrR-3-mst (3-mercaptopyruvate sulfurtransferase) operon; msrR-3-mst is divergent from multidrug efflux protein MFS. MsrR was demonstrated to bind to the intergenic region between msrR-3-mst and mfs. This binding was prevented by an MsrR oxidation-mediated increase in MsrR dimerization. MsrR was shown to use Cys62 oxidation to sense oxidative stress, resulting in its dissociation from the promoter. Elevated expression of msrR-3-mst and mfs was observed under stress. Furthermore, a ΔmsrR mutant strain displayed significantly enhanced growth, while the growth of strains lacking either 3-mst or mfs was significantly inhibited under stress. Conclusion This report is the first to demonstrate the critical role of MsrR-3-MST-MFS in bacterial stress resistance.

3-Mercaptopyruvate sulfurtransferase: an enzyme at the crossroads of sulfane sulfur trafficking

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Brandán Pedre ◽  
Tobias P. Dick
Keyword(s):  
Oxidative Stress ◽  
Metabolic Disease ◽  
Hydrogen Sulfide ◽  
Fatty Acid ◽  
Stress Resistance ◽  
Respiratory Function ◽  
Acid Metabolism ◽  
Cyanide Detoxification ◽  
Mercaptopyruvate Sulfurtransferase ◽  
Sulfur Trafficking

Abstract3-Mercaptopyruvate sulfurtransferase (MPST) catalyzes the desulfuration of 3-mercaptopyruvate to generate an enzyme-bound hydropersulfide. Subsequently, MPST transfers the persulfide’s outer sulfur atom to proteins or small molecule acceptors. MPST activity is known to be involved in hydrogen sulfide generation, tRNA thiolation, protein urmylation and cyanide detoxification. Tissue-specific changes in MPST expression correlate with ageing and the development of metabolic disease. Deletion and overexpression experiments suggest that MPST contributes to oxidative stress resistance, mitochondrial respiratory function and the regulation of fatty acid metabolism. However, the role and regulation of MPST in the larger physiological context remain to be understood.

scholarly journals NRF2 Protection against Liver Injury Produced by Various Hepatotoxicants

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Jie Liu ◽  
Kai Connie Wu ◽  
Yuan-Fu Lu ◽  
Edugie Ekuase ◽  
Curtis D. Klaassen
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Fas Ligand ◽  
Inflammatory Responses ◽  
Lithocholic Acid ◽  
Antioxidant Genes ◽  
Stress Genes ◽  
Nrf2 Activation ◽  
Genes Encoding

To investigate the role of Nrf2 as a master defense against the hepatotoxicity produced by various chemicals, Nrf2-null, wild-type, Keap1-knock down (Keap1-Kd) and Keap1-hepatocyte knockout (Keap1-HKO) mice were used as a “graded Nrf2 activation” model. Mice were treated with 14 hepatotoxicants at appropriate doses, and blood and liver samples were collected thereafter (6 h to 7 days depending on the hepatotoxicant). Graded activation of Nrf2 offered a Nrf2-dependent protection against the hepatotoxicity produced by carbon tetrachloride, acetaminophen, microcystin, phalloidin, furosemide, cadmium, and lithocholic acid, as evidenced by serum alanine aminotransferase (ALT) activities and by histopathology. Nrf2 activation also offered moderate protection against liver injury produced by ethanol, arsenic, bromobenzene, and allyl alcohol but had no effects on the hepatotoxicity produced by D-galactosamine/endotoxin and the Fas ligand antibody Jo-2. Graded Nrf2 activation reduced the expression of inflammatory genes (MIP-2, mKC, IL-1β, IL-6, and TNFα), oxidative stress genes (Ho-1, Egr1), ER stress genes (Gadd45 and Gadd153), and genes encoding cell death (Noxa, Bax, Bad, and caspase3). Thus, this study demonstrates that Nrf2 prevents the liver from many, but not all, hepatotoxicants. The Nrf2-mediated protection is accompanied by induction of antioxidant genes, suppression of inflammatory responses, and attenuation of oxidative stress.

scholarly journals Glucose Promotes Stress Resistance in the Fungal PathogenCandida albicans

2009 ◽  
Vol 20 (22) ◽  
pp. 4845-4855 ◽  
Author(s):  
Alexandra Rodaki ◽  
Iryna M. Bohovych ◽  
Brice Enjalbert ◽  
Tim Young ◽  
Frank C. Odds ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Responses ◽  
Stress Resistance ◽  
Metabolic Adaptation ◽  
Phagocytic Cells ◽  
Global Impact ◽  
Stress Genes ◽  
Glucose Levels ◽  
Metabolic Genes ◽  
Enhanced Resistance

Metabolic adaptation, and in particular the modulation of carbon assimilatory pathways during disease progression, is thought to contribute to the pathogenicity of Candida albicans. Therefore, we have examined the global impact of glucose upon the C. albicans transcriptome, testing the sensitivity of this pathogen to wide-ranging glucose levels (0.01, 0.1, and 1.0%). We show that, like Saccharomyces cerevisiae, C. albicans is exquisitely sensitive to glucose, regulating central metabolic genes even in response to 0.01% glucose. This indicates that glucose concentrations in the bloodstream (approximate range 0.05–0.1%) have a significant impact upon C. albicans gene regulation. However, in contrast to S. cerevisiae where glucose down-regulates stress responses, some stress genes were induced by glucose in C. albicans. This was reflected in elevated resistance to oxidative and cationic stresses and resistance to an azole antifungal agent. Cap1 and Hog1 probably mediate glucose-enhanced resistance to oxidative stress, but neither is essential for this effect. However, Hog1 is phosphorylated in response to glucose and is essential for glucose-enhanced resistance to cationic stress. The data suggest that, upon entering the bloodstream, C. albicans cells respond to glucose increasing their resistance to the oxidative and cationic stresses central to the armory of immunoprotective phagocytic cells.

scholarly journals The stress response protein REDD1 promotes diabetes-induced oxidative stress in the retina by Keap1-independent Nrf2 degradation

2020 ◽  
Vol 295 (21) ◽  
pp. 7350-7361 ◽  
Author(s):  
William P. Miller ◽  
Siddharth Sunilkumar ◽  
Joseph F. Giordano ◽  
Allyson L. Toro ◽  
Alistair J. Barber ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Glycogen Synthase ◽  
Critical Role ◽  
Antioxidant Response ◽  
Glycogen Synthase Kinase ◽  
Related Factor ◽  
Diabetic Mice ◽  
Antioxidant Genes ◽  
Deficient Mice

The transcription factor nuclear factor erythroid-2–related factor 2 (Nrf2) plays a critical role in reducing oxidative stress by promoting the expression of antioxidant genes. Both individuals with diabetes and preclinical diabetes models exhibit evidence of a defect in retinal Nrf2 activation. We recently demonstrated that increased expression of the stress response protein regulated in development and DNA damage 1 (REDD1) is necessary for the development of oxidative stress in the retina of streptozotocin-induced diabetic mice. In the present study, we tested the hypothesis that REDD1 suppresses the retinal antioxidant response to diabetes by repressing Nrf2 function. We found that REDD1 ablation enhances Nrf2 DNA-binding activity in the retina and that the suppressive effect of diabetes on Nrf2 activity is absent in the retina of REDD1-deficient mice compared with WT. In human MIO-M1 Müller cell cultures, REDD1 deletion prevented oxidative stress in response to hyperglycemic conditions, and this protective effect required Nrf2. REDD1 suppressed Nrf2 stability by promoting its proteasomal degradation independently of Nrf2's interaction with Kelch-like ECH-associated protein 1 (Keap1), but REDD1-mediated Nrf2 degradation required glycogen synthase kinase 3 (GSK3) activity and Ser-351/Ser-356 of Nrf2. Diabetes diminished inhibitory phosphorylation of glycogen synthase kinase 3β (GSK3β) at Ser-9 in the retina of WT mice but not in REDD1-deficient mice. Pharmacological inhibition of GSK3 enhanced Nrf2 activity and prevented oxidative stress in the retina of diabetic mice. The findings support a model wherein hyperglycemia-induced REDD1 blunts the Nrf2 antioxidant response to diabetes by activating GSK3, which, in turn, phosphorylates Nrf2 to promote its degradation.

scholarly journals Kaempferol Inhibits Zearalenone-Induced Oxidative Stress and Apoptosis via the PI3K/Akt-Mediated Nrf2 Signaling Pathway: In Vitro and In Vivo Studies

2020 ◽  
Vol 22 (1) ◽  
pp. 217
Author(s):  
Peramaiyan Rajendran ◽  
Rebai Ben Ammar ◽  
Fatma J. Al-Saeedi ◽  
Maged E. Mohamed ◽  
Medhat A. ElNaggar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Critical Role ◽  
In Vivo Studies ◽  
Marker Enzyme ◽  
Dependent Manner ◽  
In Vivo Models ◽  
Antioxidant Genes ◽  
Nrf2 Signaling Pathway

In this study, kaempferol (KFL) shows hepatoprotective activity against zearalenone (ZEA)-induced oxidative stress and its underlying mechanisms in in vitro and in vivo models were investigated. Oxidative stress plays a critical role in the pathophysiology of various hepatic ailments and is normally regulated by reactive oxygen species (ROS). ZEA is a mycotoxin known to exert toxicity via inflammation and ROS accumulation. This study aims to explore the protective role of KFL against ZEA-triggered hepatic injury via the PI3K/Akt-regulated Nrf2 pathway. KFL augmented the phosphorylation of PI3K and Akt, which may stimulate antioxidative and antiapoptotic signaling in hepatic cells. KFL upregulated Nrf2 phosphorylation and the expression of antioxidant genes HO-1 and NQO-1 in a dose-dependent manner under ZEA-induced oxidative stress. Nrf2 knockdown via small-interfering RNA (siRNA) inhibited the KFL-mediated defence against ZEA-induced hepatotoxicity. In vivo studies showed that KFL decreased inflammation and lipid peroxidation and increased H2O2 scavenging and biochemical marker enzyme expression. KFL was able to normalize the expression of liver antioxidant enzymes SOD, CAT and GSH and showed a protective effect against ZEA-induced pathophysiology in the livers of mice. These outcomes demonstrate that KFL possesses notable hepatoprotective roles against ZEA-induced damage in vivo and in vitro. These protective properties of KFL may occur through the stimulation of Nrf2/HO-1 cascades and PI3K/Akt signaling.

scholarly journals Transcription of Oxidative Stress Genes Is Directly Activated by SpxA1 and, to a Lesser Extent, by SpxA2 in Streptococcus mutans

2015 ◽  
Vol 197 (13) ◽  
pp. 2160-2170 ◽  
Author(s):  
Jessica K. Kajfasz ◽  
Isamar Rivera-Ramos ◽  
Kathleen Scott-Anne ◽  
Stacy Gregoire ◽  
Jacqueline Abranches ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oral Cavity ◽  
Streptococcus Mutans ◽  
Stress Responses ◽  
Dominant Role ◽  
Critical Role ◽  
Content Type ◽  
Stress Genes

ABSTRACTThe SpxA1 and SpxA2 (formerly SpxA and SpxB) transcriptional regulators ofStreptococcus mutansare members of a highly conserved family of proteins found inFirmicutes, and they were previously shown to activate oxidative stress responses. In this study, we showed that SpxA1 exerts substantial positive regulatory influence over oxidative stress genes following exposure to H2O2, while SpxA2 appears to have a secondary regulatory role.In vitrotranscription (IVT) assays using purified SpxA1 and/or SpxA2 showed that SpxA1 and, less often, SpxA2 directly activate transcription of some of the major oxidative stress genes. Addition of equimolar concentrations of SpxA1 and SpxA2 to the IVT reactions neither enhanced transcription of the tested genes nor disrupted the dominant role of SpxA1. Substitution of a conserved glycine residue (G52) present in both Spx proteins by arginine (SpxG52R) resulted in strains that phenocopied the Δspxstrains. Moreover, addition of purified SpxA1G52Rcompletely failed to activate transcription ofahpC,sodA, andtpx, further confirming that the G52 residue is critical for Spx functionality.IMPORTANCEStreptococcus mutansis a pathogen associated with the formation of dental caries in humans. Within the oral cavity,S. mutansroutinely encounters oxidative stress. Our previous data revealed that two regulatory proteins, SpxA1 and SpxA2 (formerly SpxA and SpxB), bear high homology to the Spx regulator that has been characterized as a critical activator of oxidative stress genes inBacillus subtilis. In this report, we prove that Spx proteins ofS. mutansdirectly activate transcription of genes involved in the oxidative stress response, though SpxA1 appears to have a more dominant role than SpxA2. Therefore, the Spx regulators play a critical role in the ability ofS. mutansto thrive within the oral cavity.

scholarly journals Loss of SigB in Listeria monocytogenes Strains EGD-e and 10403S Confers Hyperresistance to Hydrogen Peroxide in Stationary Phase under Aerobic Conditions

2016 ◽  
Vol 82 (15) ◽  
pp. 4584-4591 ◽  
Author(s):  
Marcia Boura ◽  
Ciara Keating ◽  
Kevin Royet ◽  
Ranju Paudyal ◽  
Beth O'Donoghue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Listeria Monocytogenes ◽  
Stationary Phase ◽  
Stress Resistance ◽  
Wild Type ◽  
Content Type ◽  
Stress Genes ◽  
Reverse Transcription Pcr ◽  
Stress Gene

ABSTRACTSigB is the main stress gene regulator inListeria monocytogenesaffecting the expression of more than 150 genes and thus contributing to multiple-stress resistance. Despite its clear role in most stresses, its role in oxidative stress is uncertain, as results accompanying the loss ofsigBrange from hyperresistance to hypersensitivity. Previously, these differences have been attributed to strain variation. In this study, we show conclusively that unlike for all other stresses, loss ofsigBresults in hyperresistance to H2O2(more than 8 log CFU ml−1compared to the wild type) in aerobically grown stationary-phase cultures ofL. monocytogenesstrains 10403S and EGD-e. Furthermore, growth at 30°C resulted in higher resistance to oxidative stress than that at 37°C. Oxidative stress resistance seemed to be higher with higher levels of oxygen. Under anaerobic conditions, the loss of SigB in 10403S did not affect survival against H2O2, while in EGD-e, it resulted in a sensitive phenotype. During exponential phase, minor differences occurred, and this result was expected due to the absence ofsigBtranscription. Catalase tests were performed under all conditions, and stronger catalase results corresponded well with a higher survival rate, underpinning the important role of catalase in this phenotype. Furthermore, we assessed the catalase activity in protein lysates, which corresponded with the catalase tests and survival. In addition, reverse transcription-PCR (RT-PCR) showed no differences in transcription between the wild type and the ΔsigBmutant in various oxidative stress genes. Further investigation of the molecular mechanism behind this phenotype and its possible consequences for the overall phenotype ofL. monocytogenesare under way.IMPORTANCESigB is the most important stress gene regulator inL. monocytogenesand other Gram-positive bacteria. Its increased expression during stationary phase results in resistance to multiple stresses. However, despite its important role in general stress resistance, its expression is detrimental for the cell in the presence of oxidative stress, as it promotes hypersensitivity against hydrogen peroxide. This peculiar phenotype is an important element of the physiology ofL. monocytogenes, and it might help us explain the behavior of this organism in environments where oxidative stress is present.

The importance and significance of gene polymorphisms in preeclampsia

2016 ◽  
pp. 45-49
Author(s):  
P.N. Veropotvelyan ◽  
◽  
I.S. Tsehmistrenko ◽  
N.P. Veropotvelyan ◽  
N.S. Rusak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Systematic Review ◽  
Early Diagnosis ◽  
Gene Polymorphisms ◽  
Individual Risk ◽  
Extended Study ◽  
Stress Genes ◽  
Detoxification System ◽  
The Individual ◽  
The Relationship

Was to conduct a systematic review of data on the relationship between polymorphisms genes of detoxification system and development of preeclampsia (РЕ). Рresents the main genes of detoxification system (GSTPI, GSTМI, GSTТI, GРХI, ЕРНХI, SOD-2, SOD-3, CYPIAL, MTHЕR, MTR) and their functions. Of interest is the possibility of calculating the individual risk of PE based on the results about the presence of a combination of different polymorphisms in the genotype of the female. Question about early diagnosis of РЕ remains controversial and not fully understood. It is necessary to conduct further in-depth, extended study of this problem. Key words: preeclampsia, oxidative stress, genes of the detoxification system.

LncRNA SNHG12 Improves Cerebral Ischemic-reperfusion Injury by Activating SIRT1/FOXO3a Pathway through I nhibition of Autophagy and Oxidative Stress

2020 ◽  
Vol 17 (4) ◽  
pp. 394-401
Author(s):  
Yuanhua Wu ◽  
Yuan Huang ◽  
Jing Cai ◽  
Donglan Zhang ◽  
Shixi Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Cell Activity ◽  
Ht22 Cells ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Reperfusion ◽  
And Oxidative Stress

Background: Ischemia/reperfusion (I/R) injury involves complex biological processes and molecular mechanisms such as autophagy. Oxidative stress plays a critical role in the pathogenesis of I/R injury. LncRNAs are the regulatory factor of cerebral I/R injury. Methods: This study constructs cerebral I/R model to investigate role of autophagy and oxidative stress in cerebral I/R injury and the underline regulatory mechanism of SIRT1/ FOXO3a pathway. In this study, lncRNA SNHG12 and FOXO3a expression was up-regulated and SIRT1 expression was down-regulated in HT22 cells of I/R model. Results: Overexpression of lncRNA SNHG12 significantly increased the cell viability and inhibited cerebral ischemicreperfusion injury induced by I/Rthrough inhibition of autophagy. In addition, the transfected p-SIRT1 significantly suppressed the release of LDH and SOD compared with cells co-transfected with SIRT1 and FOXO3a group and cells induced by I/R and transfected with p-SNHG12 group and overexpression of cells co-transfected with SIRT1 and FOXO3 further decreased the I/R induced release of ROS and MDA. Conclusion: In conclusion, lncRNA SNHG12 increased cell activity and inhibited oxidative stress through inhibition of SIRT1/FOXO3a signaling-mediated autophagy in HT22 cells of I/R model. This study might provide new potential therapeutic targets for further investigating the mechanisms in cerebral I/R injury and provide.

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