scholarly journals Overexpression of Mycothiol Disulfide Reductase Enhances Corynebacterium glutamicum Robustness by Modulating Cellular Redox Homeostasis and Antioxidant Proteins under Oxidative Stress

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Meiru Si ◽  
Chao Zhao ◽  
Bing Zhang ◽  
Dawei Wei ◽  
Keqi Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Corynebacterium Glutamicum ◽  
Redox Homeostasis ◽  
Cellular Redox ◽  
Disulfide Reductase ◽  
Antioxidant Proteins

scholarly journals Endogenous formaldehyde scavenges cellular glutathione resulting in cytotoxic redox disruption

2020 ◽  
Author(s):  
Carla Umansky ◽  
Agustín Morellato ◽  
Marco Scheidegger ◽  
Matthias Rieckher ◽  
Manuela R. Martinefski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Repair ◽  
Fanconi Anemia ◽  
Redox Homeostasis ◽  
Thiol Group ◽  
Cellular Damage ◽  
Repair Pathway ◽  
Cellular Redox ◽  
Redox Active ◽  
Development And Aging

AbstractFormaldehyde (FA) is a ubiquitous endogenous and environmental metabolite that is thought to exert cytotoxicity through DNA and DNA-protein crosslinking. We show here that FA can cause cellular damage beyond genotoxicity by triggering oxidative stress, which is prevented by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR). Mechanistically, we determine that endogenous FA reacts with the redox-active thiol group of glutathione (GSH) forming S-hydroxymethyl-GSH, which is metabolized by ADH5 yielding reduced GSH thus preventing redox disruption. We identify the ADH5-ortholog gene in Caenorhabditis elegans and show that oxidative stress also underlies FA toxicity in nematodes. Moreover, we show that endogenous GSH can protect cells lacking the Fanconi Anemia DNA repair pathway from FA, which might have broad implications for Fanconi Anemia patients and for healthy BRCA2-mutation carriers. We thus establish a highly conserved mechanism through which endogenous FA disrupts the GSH-regulated cellular redox homeostasis that is critical during development and aging.

scholarly journals Gankyrin has an antioxidative role through the feedback regulation of Nrf2 in hepatocellular carcinoma

2016 ◽  
Vol 213 (5) ◽  
pp. 859-875 ◽  
Author(s):  
Chun Yang ◽  
Ye-xiong Tan ◽  
Guang-zhen Yang ◽  
Jian Zhang ◽  
Yu-fei Pan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepatocellular Carcinoma ◽  
Redox Homeostasis ◽  
Feedback Regulation ◽  
Cellular Redox ◽  
Intracellular Ros ◽  
Oxidative Stress Status ◽  
Kelch Domain ◽  
Cellular Stressors ◽  
Hcc Cells

Oxidative stress status has a key role in hepatocellular carcinoma (HCC) development and progression. Normally, reactive oxygen species (ROS) levels are tightly controlled by an inducible antioxidant program that responds to cellular stressors. How HCC cells respond to excessive oxidative stress remains elusive. Here, we identified a feedback loop between gankyrin, an oncoprotein overexpressed in human HCC, and Nrf2 maintaining the homeostasis in HCC cells. Mechanistically, gankyrin was found to interact with the Kelch domain of Keap1 and effectively competed with Nrf2 for Keap1 binding. Increased expression of gankyrin in HCC cells blocked the binding between Nrf2 and Keap1, inhibiting the degradation of Nrf2 by proteasome. Interestingly, accumulation and translocation of Nrf2 increased the transcription of gankyrin through binding to the ARE elements in the promoter of gankyrin. The positive feedback regulation involving gankyrin and Nrf2 modulates a series of antioxidant enzymes, thereby lowering intracellular ROS and conferring a steadier intracellular environment, which prevents mitochondrial damage and cell death induced by excessive oxidative stress. Our results indicate that gankyrin is a regulator of cellular redox homeostasis and provide a link between oxidative stress and the development of HCC.

scholarly journals Identification, Characterization, and Stress Responsiveness of Glucose-6-phosphate Dehydrogenase Genes in Highland Barley

Plants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1800
Author(s):  
Ruijun Feng ◽  
Xiaomin Wang ◽  
Li He ◽  
Shengwang Wang ◽  
Junjie Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Redox Homeostasis ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reducing Power ◽  
Cellular Redox ◽  
E Coli ◽  
Intermediate Metabolites ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Highland Barley ◽  
Salt And Drought Stresses

G6PDH provides intermediate metabolites and reducing power (nicotinamide adenine dinucleotide phosphate, NADPH) for plant metabolism, and plays a pivotal role in the cellular redox homeostasis. In this study, we cloned five G6PDH genes (HvG6PDH1 to HvG6PDH5) from highland barley and characterized their encoded proteins. Functional analysis of HvG6PDHs in E. coli showed that HvG6PDH1 to HvG6PDH5 encode the functional G6PDH proteins. Subcellular localization and phylogenetic analysis indicated that HvG6PDH2 and HvG6PDH5 are localized in the cytoplasm, while HvG6PDH1, HvG6PDH3, and HvG6PDH4 are plastidic isoforms. Analysis of enzymatic activities and gene expression showed that HvG6PDH1 to HvG6PDH4 are involved in responses to salt and drought stresses. The cytosolic HvG6PDH2 is the major isoform against oxidative stress. HvG6PDH5 may be a house-keeping gene. In addition, HvG6PDH1 to HvG6PDH4 and their encoded enzymes responded to jasmonic acid (JA) and abscisic acid (ABA) treatments, implying that JA and ABA are probably critical regulators of HvG6PDHs (except for HvG6PDH5). Reactive oxygen species analysis showed that inhibition of cytosolic and plastidic G6PDH activities leads to increased H2O2 and O2− contents in highland barley under salt and drought stresses. These results suggest that G6PDH can maintain cellular redox homeostasis and that cytosolic HvG6PDH2 is an irreplaceable isoform against oxidative stress in highland barley.

scholarly journals Nestin regulates cellular redox homeostasis in lung cancer through the Keap1–Nrf2 feedback loop

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jiancheng Wang ◽  
Qiying Lu ◽  
Jianye Cai ◽  
Yi Wang ◽  
Xiaofan Lai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Cancer ◽  
Feedback Loop ◽  
Redox Homeostasis ◽  
Antioxidant Response ◽  
Cellular Redox ◽  
Anti Cancer ◽  
Oxidative Stress Status ◽  
Kelch Domain ◽  
Antioxidant Response Elements

Abstract Abnormal cancer antioxidant capacity is considered as a potential mechanism of tumor malignancy. Modulation of oxidative stress status is emerging as an anti-cancer treatment. Our previous studies have found that Nestin-knockdown cells were more sensitive to oxidative stress in non-small cell lung cancer (NSCLC). However, the molecular mechanism by which Nestin protects cells from oxidative damage remains unclear. Here, we identify a feedback loop between Nestin and Nrf2 maintaining the redox homeostasis. Mechanistically, the ESGE motif of Nestin interacts with the Kelch domain of Keap1 and competes with Nrf2 for Keap1 binding, leading to Nrf2 escaping from Keap1-mediated degradation, subsequently promoting antioxidant enzyme generation. Interestingly, we also map that the antioxidant response elements (AREs) in the Nestin promoter are responsible for its induction via Nrf2. Taken together, our results indicate that the Nestin–Keap1–Nrf2 axis regulates cellular redox homeostasis and confers oxidative stress resistance in NSCLC.

scholarly journals Understanding Cellular Redox Homeostasis: A Challenge for Precision Medicine

2021 ◽  
Vol 23 (1) ◽  
pp. 106
Author(s):  
Verena Tretter ◽  
Beatrix Hochreiter ◽  
Marie Louise Zach ◽  
Katharina Krenn ◽  
Klaus Ulrich Klein
Keyword(s):  
Oxidative Stress ◽  
Precision Medicine ◽  
Redox Homeostasis ◽  
Reactive Species ◽  
Scientific Field ◽  
Redox Systems ◽  
Cellular Redox ◽  
Redox Biology ◽  
Living Organisms ◽  
Large Repertoire

Living organisms use a large repertoire of anabolic and catabolic reactions to maintain their physiological body functions, many of which include oxidation and reduction of substrates. The scientific field of redox biology tries to understand how redox homeostasis is regulated and maintained and which mechanisms are derailed in diverse pathological developments of diseases, where oxidative or reductive stress is an issue. The term “oxidative stress” is defined as an imbalance between the generation of oxidants and the local antioxidative defense. Key mediators of oxidative stress are reactive species derived from oxygen, nitrogen, and sulfur that are signal factors at physiological concentrations but can damage cellular macromolecules when they accumulate. However, therapeutical targeting of oxidative stress in disease has proven more difficult than previously expected. Major reasons for this are the very delicate cellular redox systems that differ in the subcellular compartments with regard to their concentrations and depending on the physiological or pathological status of cells and organelles (i.e., circadian rhythm, cell cycle, metabolic need, disease stadium). As reactive species are used as signaling molecules, non-targeted broad-spectrum antioxidants in many cases will fail their therapeutic aim. Precision medicine is called to remedy the situation.

scholarly journals Synchronization and interaction of proline, ascorbate and oxidative stress pathways under abiotic stress combination in tomato plants

2020 ◽  
Author(s):  
María Lopez-Delacalle ◽  
Christian J Silva ◽  
Teresa C Mestre ◽  
Vicente Martinez ◽  
Barbara Blanco-Ulate ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Metabolic Pathways ◽  
Leucine Zipper ◽  
Redox Homeostasis ◽  
Basic Leucine Zipper ◽  
Cellular Redox ◽  
Tomato Plants ◽  
Leucine Zipper Domain ◽  
And Oxidative Stress

ABSTRACTAdverse environmental conditions have a devastating impact on plant productivity. In nature, multiple abiotic stresses occur simultaneously, and plants have evolved unique responses to cope against this combination of stresses. Here, we coupled genome-wide transcriptional profiling and untargeted metabolomics with physiological and biochemical analyses to characterize the effect of salinity and heat applied in combination on the metabolism of tomato plants. Our results demonstrate that this combination of stresses causes a unique reprogramming of metabolic pathways, including changes in the expression of 1,388 genes and the accumulation of 568 molecular features. Pathway enrichment analysis of transcript and metabolite data indicated that the proline and ascorbate pathways act synchronously to maintain cellular redox homeostasis, which was supported by measurements of enzymatic activity and oxidative stress markers. We also identified key transcription factors from the basic Leucine Zipper Domain (bZIP), Zinc Finger Cysteine-2/Histidine-2 (C2H2) and Trihelix families that are likely regulators of the identified up-regulated genes under salinity+heat combination. Our results expand the current understanding of how plants acclimate to environmental stresses in combination and unveils the synergy between key cellular metabolic pathways for effective ROS detoxification. Our study opens the door to elucidating the different signaling mechanisms for stress tolerance.HIGHLIGHTSThe combination of salinity and heat causes a unique reprogramming of tomato metabolic pathways by changing the expression of specific genes and metabolic features.Proline and ascorbate pathways act synchronously to maintain cellular redox homeostasisKey transcription factors from the basic Leucine Zipper Domain (bZIP), Zinc Finger Cysteine-2/Histidine-2 (C2H2) and Trihelix families were identified as putative regulators of the identified up-regulated genes under salinity and heat combination.

scholarly journals Staphylococcus aureususes the bacilliredoxin (BrxAB)/ bacillithiol disulfide reductase (YpdA) redox pathway to defend against oxidative stress under infections

2019 ◽  
Author(s):  
Nico Linzner ◽  
Vu Van Loi ◽  
Verena Nadin Fritsch ◽  
Quach Ngoc Tung ◽  
Saskia Stenzel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanism ◽  
Redox Homeostasis ◽  
Stress Monitoring ◽  
Macrophage Infection ◽  
Disulfide Reductase ◽  
Mixed Disulfides

ABSTRACTStaphylococcus aureusis a major human pathogen and has to cope with reactive oxygen and chlorine species (ROS, RCS) during infections. The low molecular weight thiol bacillithiol (BSH) is an important defense mechanism ofS. aureusfor detoxification of ROS and HOCl stress to maintain the reduced state of the cytoplasm. Under HOCl stress, BSH forms mixed disulfides with proteins, termed asS-bacillithiolations, which are reduced by bacilliredoxins (BrxA and BrxB). The NADPH-dependent flavin disulfide reductase YpdA is phylogenetically associated with the BSH synthesis and BrxA/B enzymes and was proposed to function as BSSB reductase. Here, we investigated the role of the bacilliredoxin BrxAB/BSH/YpdA pathway inS. aureusCOL under oxidative stress and macrophage infection conditionsin vivoand in biochemical assaysin vitro. Using HPLC thiol metabolomics, a strongly enhanced BSSB level and a decreased BSH/BSSB ratio were measured in theS. aureusCOLypdAdeletion mutant under control and NaOCl stress. Monitoring the BSH redox potential (EBSH) using the Brx-roGFP2 biosensor revealed that YpdA is required for regeneration of the reducedEBSHupon recovery from oxidative stress. In addition, theypdAmutant was impaired in H2O2detoxification as measured with the novel H2O2-specific Tpx-roGFP2 biosensor. Phenotype analyses further showed that BrxA and YpdA are required for survival under NaOCl and H2O2stressin vitroand inside murine J-774A.1 macrophages in infection assaysin vivo. Finally, NADPH-coupled electron transfer assays provide evidence for the function of YpdA in BSSB reduction, which depends on the conserved Cys14 residue. YpdA acts together with BrxA and BSH in de-bacillithiolation ofS-bacilithiolated GapDH. In conclusion, our results point to a major role of the BrxA/BSH/YpdA pathway in BSH redox homeostasis inS. aureusduring recovery from oxidative stress and under infections.

The Role of Selenium in Oxidative Stress and in Nonthyroidal Illness Syndrome (NTIS): An Overview

2020 ◽  
Vol 27 (3) ◽  
pp. 423-449 ◽  
Author(s):  
Andrea Silvestrini ◽  
Alvaro Mordente ◽  
Giuseppe Martino ◽  
Carmine Bruno ◽  
Edoardo Vergani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Redox Homeostasis ◽  
Nonthyroidal Illness ◽  
Cellular Redox ◽  
Selenium Metabolism ◽  
Glutathione Peroxidases ◽  
Iodothyronine Deiodinases ◽  
Correct Function ◽  
Thioredoxin Reductases

Selenium is a trace element, nutritionally classified as an essential micronutrient, involved in maintaining the correct function of several enzymes incorporating the selenocysteine residue, namely the selenoproteins. The human selenoproteome including 25 proteins is extensively described here. The most relevant selenoproteins, including glutathione peroxidases, thioredoxin reductases and iodothyronine deiodinases are required for the proper cellular redox homeostasis as well as for the correct thyroid function, thus preventing oxidative stress and related diseases. This review summarizes the main advances on oxidative stress with a focus on selenium metabolism and transport. Moreover, thyroid-related disorders are discussed, considering that the thyroid gland contains the highest selenium amount per gram of tissue, also for future possible therapeutic implication.

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