scholarly journals Interaction of Hydrogen Sulfide with Oxygen Sensing under Hypoxia

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Bo Wu ◽  
Huajian Teng ◽  
Li Zhang ◽  
Hong Li ◽  
Jing Li ◽  
...  
Keyword(s):  
Target Genes ◽  
Oxygen Sensing ◽  
Protective Role ◽  
Hypoxia Inducible Factors ◽  
Enzymatic Production ◽  
Hypoxic Conditions ◽  
Carotid Bodies ◽  
Genes Expression ◽  
Mercaptopyruvate Sulfurtransferase

Based on the discovery of endogenous H2S production, many in depth studies show this gasotransmitter with a variety of physiological and pathological functions. Three enzymes, cystathionineβ-synthase (CBS), cystathionineγ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MST), are involved in enzymatic production of H2S. Emerging evidence has elucidated an important protective role of H2S in hypoxic conditions in many mammalian systems. However, the mechanisms by which H2S senses and responses to hypoxia are largely elusive. Hypoxia-inducible factors (HIFs) function as key regulators of oxygen sensing, activating target genes expression under hypoxia. Recent studies have shown that exogenous H2S regulates HIF action in different patterns. The activation of carotid bodies is a sensitive and prompt response to hypoxia, rapidly enhancing general O2supply. H2S has been identified as an excitatory mediator of hypoxic sensing in the carotid bodies. This paper presents a brief review of the roles of these two pathways which contribute to hypoxic sensing of H2S.

scholarly journals Hypoxia and the Receptor for Advanced Glycation End Products (RAGE) Signaling in Cancer

2021 ◽  
Vol 22 (15) ◽  
pp. 8153
Author(s):  
Sakshi Taneja ◽  
Stefan W. Vetter ◽  
Estelle Leclerc
Keyword(s):  
Advanced Glycation End Products ◽  
Cellular Response ◽  
Target Genes ◽  
Tumor Biology ◽  
Hypoxia Inducible Factors ◽  
Advanced Glycation ◽  
Hypoxic Conditions ◽  
Glycation End Products ◽  
End Products

Hypoxia is characterized by an inadequate supply of oxygen to tissues, and hypoxic regions are commonly found in solid tumors. The cellular response to hypoxic conditions is mediated through the activation of hypoxia-inducible factors (HIFs) that control the expression of a large number of target genes. Recent studies have shown that the receptor for advanced glycation end products (RAGE) participates in hypoxia-dependent cellular adaptation. We review recent evidence on the role of RAGE signaling in tumor biology under hypoxic conditions.

scholarly journals Protective role of estrogen against excessive erythrocytosis in Monge’s disease

2021 ◽  
Vol 53 (1) ◽  
pp. 125-135
Author(s):  
Priti Azad ◽  
Francisco C. Villafuerte ◽  
Daniela Bermudez ◽  
Gargi Patel ◽  
Gabriel G. Haddad
Keyword(s):  
High Altitude ◽  
Messenger Rna ◽  
Target Genes ◽  
Protective Role ◽  
Mrna Levels ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Andean Population

AbstractMonge’s disease (chronic mountain sickness (CMS)) is a maladaptive condition caused by chronic (years) exposure to high-altitude hypoxia. One of the defining features of CMS is excessive erythrocytosis with extremely high hematocrit levels. In the Andean population, CMS prevalence is vastly different between males and females, being rare in females. Furthermore, there is a sharp increase in CMS incidence in females after menopause. In this study, we assessed the role of sex hormones (testosterone, progesterone, and estrogen) in CMS and non-CMS cells using a well-characterized in vitro erythroid platform. While we found that there was a mild (nonsignificant) increase in RBC production with testosterone, we observed that estrogen, in physiologic concentrations, reduced sharply CD235a+ cells (glycophorin A; a marker of RBC), from 56% in the untreated CMS cells to 10% in the treated CMS cells, in a stage-specific and dose-responsive manner. At the molecular level, we determined that estrogen has a direct effect on GATA1, remarkably decreasing the messenger RNA (mRNA) and protein levels of GATA1 (p < 0.01) and its target genes (Alas2, BclxL, and Epor, p < 0.001). These changes result in a significant increase in apoptosis of erythroid cells. We also demonstrate that estrogen regulates erythropoiesis in CMS patients through estrogen beta signaling and that its inhibition can diminish the effects of estrogen by significantly increasing HIF1, VEGF, and GATA1 mRNA levels. Taken altogether, our results indicate that estrogen has a major impact on the regulation of erythropoiesis, particularly under chronic hypoxic conditions, and has the potential to treat blood diseases, such as high altitude severe erythrocytosis.

scholarly journals The protective role of the 3-mercaptopyruvate sulfurtransferase (3-MST)-hydrogen sulfide (H2S) pathway against experimental osteoarthritis

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Sonia Nasi ◽  
Driss Ehirchiou ◽  
Athanasia Chatzianastasiou ◽  
Noriyuki Nagahara ◽  
Andreas Papapetropoulos ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Protective Role ◽  
Mercaptopyruvate Sulfurtransferase ◽  
Experimental Osteoarthritis

scholarly journals NQO1 binds and supports SIRT1 function

2017 ◽  
Author(s):  
Peter Tsvetkov ◽  
Julia Adler ◽  
Yaarit Adamovich ◽  
Gad Asher ◽  
Nina Reuven ◽  
...  
Keyword(s):  
Target Genes ◽  
Protective Role ◽  
Class Iii ◽  
Mitochondrial Stress ◽  
Protein Levels ◽  
Related Enzyme ◽  
Metabolic Sensing ◽  
Regulatory Loop ◽  
Nadh Oxidoreductase

AbstractSilent information regulator 2-related enzyme 1 (SIRT1) is an NAD+-dependent class III deacetylase and a key component of the cellular metabolic sensing pathway. The requirement of NAD+ for SIRT1 activity led us to assume that NQO1, an NADH oxidoreductase producing NAD+, regulates SIRT1 activity. We show here that SIRT1 is capable of increasing NQO1 (NAD(P)H Dehydrogenase Quinone 1) transcription and protein levels. NQO1 physically interacts with SIRT1 but not with an enzymatically dead SIRT1 H363Y mutant. The interaction of NQO1 with SIRT1 is markedly increased under mitochondrial inhibition. Interestingly, under this condition the nuclear pool of NQO1 is elevated. Depletion of NQO1 compromises the role of SIRT1 in inducing transcription of several target genes and eliminates the protective role of SIRT1 following mitochondrial inhibition. Our results suggest that SIRT1 and NQO1 form a regulatory loop where SIRT1 regulates NQO1 expression and NQO1 binds and mediates the protective role of SIRT1 during mitochondrial stress. The interplay between an NADH oxidoreductase enzyme and an NAD+ dependent deacetylase may act as a rheostat in sensing mitochondrial stress.

scholarly journals The role of hypoxia-inducible factors in the development of chronic pathology

2021 ◽  
Vol 93 (4) ◽  
pp. 18-25
Author(s):  
N. S. Shevchenko ◽  
◽  
N. V. Krutenko ◽  
T. V. Zimnytska ◽  
K. V. Voloshyn ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Chronic Diseases ◽  
Inflammatory Process ◽  
Metabolic Disorders ◽  
Current Understanding ◽  
Human Organism ◽  
Hypoxia Inducible Factors ◽  
Significant Relationships ◽  
Genes Expression

This review highlights the current understanding of hypoxia-inducible factors (HIFs) role as regulators of oxygen-dependent reactions and inducers of genes expression in human organism. The focus is on the most significant relationships between the activation or inhibition of the HIFs intracellular system and development of the inflammatory process in various organs, chronic diseases of gastrointestinal tract, osteoarticular system, kidneys as well as hematological, endocrine and metabolic disorders.

scholarly journals Role of the Nrf2-ARE Pathway in Liver Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Sang Mi Shin ◽  
Ji Hye Yang ◽  
Sung Hwan Ki
Keyword(s):  
Liver Diseases ◽  
Target Genes ◽  
Antioxidant Response ◽  
Related Factor ◽  
Genes Expression ◽  
Wide Range ◽  
Range Of Functions ◽  
Central Organ ◽  
Essential Transcription Factor

The liver is a central organ that performs a wide range of functions such as detoxification and metabolic homeostasis. Since it is a metabolically active organ, liver is particularly susceptible to oxidative stress. It is well documented that liver diseases including hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma are highly associated with antioxidant capacity. NF-E2-related factor-2 (Nrf2) is an essential transcription factor that regulates an array of detoxifying and antioxidant defense genes expression in the liver. It is activated in response to electrophiles and induces its target genes by binding to the antioxidant response element (ARE). Therefore, the roles of the Nrf2-ARE pathway in liver diseases have been extensively investigated. Studies from several animal models suggest that the Nrf2-ARE pathway collectively exhibits diverse biological functions against viral hepatitis, alcoholic and nonalcoholic liver disease, fibrosis, and cancer via target gene expression. In this review, we will discuss the role of the Nrf2-ARE pathway in liver pathophysiology and the potential application of Nrf2 as a therapeutic target to prevent and treat liver diseases.

scholarly journals Oxidative stress-induced FABP5 S-glutathionylation protects against acute lung injury by suppressing inflammation in macrophages

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuxian Guo ◽  
Yaru Liu ◽  
Shihao Zhao ◽  
Wangting Xu ◽  
Yiqing Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Target Genes ◽  
Nuclear Translocation ◽  
Protein S ◽  
Protective Role ◽  
Fatty Acid Binding ◽  
Proteomics Approach

AbstractOxidative stress contributes to the pathogenesis of acute lung injury. Protein S-glutathionylation plays an important role in cellular antioxidant defense. Here we report that the expression of deglutathionylation enzyme Grx1 is decreased in the lungs of acute lung injury mice. The acute lung injury induced by hyperoxia or LPS is significantly relieved in Grx1 KO and Grx1fl/flLysMcre mice, confirming the protective role of Grx1-regulated S-glutathionylation in macrophages. Using a quantitative redox proteomics approach, we show that FABP5 is susceptible to S-glutathionylation under oxidative conditions. S-glutathionylation of Cys127 in FABP5 promotes its fatty acid binding ability and nuclear translocation. Further results indicate S-glutathionylation promotes the interaction of FABP5 and PPARβ/δ, activates PPARβ/δ target genes and suppresses the LPS-induced inflammation in macrophages. Our study reveals a molecular mechanism through which FABP5 S-glutathionylation regulates macrophage inflammation in the pathogenesis of acute lung injury.

scholarly journals Mammalian oxygen sensing, signalling and gene regulation

2000 ◽  
Vol 203 (8) ◽  
pp. 1253-1263 ◽  
Author(s):  
R.H. Wenger
Keyword(s):  
Oxygen Supply ◽  
Oxygen Sensing ◽  
Beta Subunit ◽  
Hypoxia Inducible Factors ◽  
Cell Type ◽  
Hypoxic Conditions ◽  
Oxygen Homeostasis ◽  
Number Of Genes ◽  
Made In ◽  
Limited Oxygen

Oxygen is essential to the life of all aerobic organisms. Virtually every cell type is able to sense a limited oxygen supply (hypoxia) and specifically to induce a set of oxygen-regulated genes. This review summarizes current concepts of mammalian oxygen-sensing and signal-transduction pathways. Since the discovery of the hypoxia-inducible factors (HIFs), a great deal of progress has been made in our comprehension of how hypoxia induces the expression of oxygen-regulated genes. The alpha subunit of the heterodimeric transcription factors HIF-1, 2 and 3 is unstable under normoxia but is rapidly stabilized upon exposure to hypoxic conditions. Following heterodimerization with the constitutively expressed beta subunit, HIFs activate the transcription of an increasing number of genes involved in maintaining oxygen homeostasis at the cellular, local and systemic levels.

scholarly journals NQO1 Binds and Supports SIRT1 Function

2021 ◽  
Vol 12 ◽  
Author(s):  
Peter Tsvetkov ◽  
Julia Adler ◽  
Romano Strobelt ◽  
Yaarit Adamovich ◽  
Gad Asher ◽  
...  
Keyword(s):  
Target Genes ◽  
Protective Role ◽  
Class Iii ◽  
Mitochondrial Stress ◽  
Protein Levels ◽  
Related Enzyme ◽  
Metabolic Sensing ◽  
Regulatory Loop ◽  
Nadh Oxidoreductase

Silent information regulator 2-related enzyme 1 (SIRT1) is an NAD+-dependent class III deacetylase and a key component of the cellular metabolic sensing pathway. The requirement of NAD+ for SIRT1 activity led us to assume that NQO1, an NADH oxidoreductase producing NAD+, regulates SIRT1 activity. We show here that SIRT1 is capable of increasing NQO1 (NAD(P)H Dehydrogenase Quinone 1) transcription and protein levels. NQO1 physically interacts with SIRT1 but not with an enzymatically dead SIRT1 H363Y mutant. The interaction of NQO1 with SIRT1 is markedly increased under mitochondrial inhibition. Interestingly, under this condition the nuclear pool of NQO1 is elevated. Depletion of NQO1 compromises the role of SIRT1 in inducing transcription of several target genes and eliminates the protective role of SIRT1 following mitochondrial inhibition. Our results suggest that SIRT1 and NQO1 form a regulatory loop where SIRT1 regulates NQO1 expression and NQO1 binds and mediates the protective role of SIRT1 during mitochondrial stress. The interplay between an NADH oxidoreductase enzyme and an NAD+ dependent deacetylase may act as a rheostat in sensing mitochondrial stress.

Upregulation of Nrf2-related cytoprotective genes expression by acetaminophen-induced acute hepatotoxicity in mice and the protective role of betaine

2020 ◽  
Vol 39 (7) ◽  
pp. 948-959 ◽  
Author(s):  
MJ Khodayar ◽  
H Kalantari ◽  
L Khorsandi ◽  
M Rashno ◽  
L Zeidooni
Keyword(s):  
Western Blot ◽  
Real Time ◽  
Liver Toxicity ◽  
Protective Role ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Compensatory Mechanism ◽  
Genes Expression ◽  
Transsulfuration Pathway

Overdose of acetaminophen (APAP) is the main reason for acute liver failure. Oxidative stress is associated with hepatotoxicity caused by APAP. Betaine is a methyl donor and S-adenosylmethionine precursor. The present study investigated the effect of betaine and the role of nuclear factor-erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) genes in hepatotoxicity induced by APAP in mice. In this study, male Naval Medical Research Institute (NMRI) mice were treated with 500 mg/kg of betaine for 5 days followed with a single dose of APAP 300 mg/kg on the fifth day. Biochemical, histological, immunohistochemical, Western blot, and real-time polymerase chain reaction (PCR) analyses were then conducted. The results of the present study showed that betaine pretreatment improved hepatotoxicity through the reduction of serum ALT and AST levels and ameliorating histopathological finding. Betaine pretreatment also increased glutathione level and decreased malondialdehyde level. Importantly, the results of immunohistochemical, Western blot and real-time PCR showed that the APAP increased the expression of the genes and proteins of Nrf2 and HO-1. While betaine decreased Nrf2 and HO-1 expression in comparison with the APAP group. The findings of this study demonstrated that the increased expression of Nrf2 and HO-1 genes and proteins by APAP is a compensatory mechanism to combat acute liver toxicity. While the protective effect of betaine against acute liver injury induced by APAP is independent on the Nrf2 and HO-1 genes but occurs via modifying cysteine supply as a precursor of glutathione in the transsulfuration pathway in the liver.

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