scholarly journals HIF1α stabilization in hypoxia is not oxidant-initiated

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Amit Kumar ◽  
Manisha Vaish ◽  
Saravanan S Karuppagounder ◽  
Irina Gazaryan ◽  
John W Cave ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Antioxidant Enzymes ◽  
Glutathione Peroxidase ◽  
Protein Stability ◽  
Lipid Peroxides ◽  
Second Messenger ◽  
Hypoxic Adaptation

Hypoxic adaptation mediated by HIF transcription factors requires mitochondria, which have been implicated in regulating HIF1α stability in hypoxia by distinct models that involve consuming oxygen or alternatively converting oxygen into the second messenger peroxide. Here, we use a ratiometric, peroxide reporter, HyPer to evaluate the role of peroxide in regulating HIF1α stability. We show that antioxidant enzymes are neither homeostatically induced nor are peroxide levels increased in hypoxia. Additionally, forced expression of diverse antioxidant enzymes, all of which diminish peroxide, had disparate effects on HIF1α protein stability. Moreover, decrease in lipid peroxides by glutathione peroxidase-4 or superoxide by mitochondrial SOD, failed to influence HIF1α protein stability. These data show that mitochondrial, cytosolic or lipid ROS were not necessary for HIF1α stability, and favor a model where mitochondria contribute to hypoxic adaptation as oxygen consumers.

scholarly journals Lipid Peroxides and Antioxidant Enzymes in Cisplatin-Induced Chronic Nephrotoxicity in Rats

2005 ◽  
Vol 2005 (3) ◽  
pp. 139-143 ◽  
Author(s):  
Ricardo González ◽  
Cheyla Romay ◽  
Aluet Borrego ◽  
Frank Hernández ◽  
Nelson Merino ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Antioxidant Enzymes ◽  
Glutathione Peroxidase ◽  
Antioxidant System ◽  
Renal Damage ◽  
Lipid Peroxides ◽  
Thiobarbituric Acid ◽  
Thiobarbituric Acid Reactive Substances ◽  
Repeated Doses

Cisplatin (CDDP), an anticancer drug, induces remarkable toxicity in the kidneys of animals and humans and it has been well documented that reactive oxygen species and the renal antioxidant system are strongly involved in acute renal damage induced by CDDP. The aim of the present study was to investigate whether or not the renal antioxidant system plays also an important role in chronic renal damage induced by repeated doses of CDDP (1 mg/kg intraperitoneally twice weekly during 10 weeks in rats). In order to elucidate it, serum creatinine and urea levels, renal glutathione and thiobarbituric acid-reactive substances (TBARS) content, as well as renal superoxide dismutase and glutathione peroxidase activities were measured in the kidney homogenates of chronically CDDP-treated rats and additionally histological studies were performed in the rat kidneys. The chronic treatment with CDDP induced a significant increase in creatinine and urea levels in serum, but the other parameters mentioned above were not significantly modified as compared to the values in nontreated rats. Taking into account these results, we conclude that chronic CDDP administration induces also severe nephrotoxicity, in contrast to CDDP acute application, without any significant modification in the activity of relevant antioxidant enzymes such as superoxide dismutase and glutathione peroxidase, renal glutathione and lipid peroxides, by which the role of the antioxidant system in chronic nephrotoxicity induced by CDDP in rats is uncertain.

scholarly journals Oxidants are dispensable for HIF1α stability in hypoxia

2020 ◽  
Author(s):  
Amit Kumar ◽  
Manisha Vaish ◽  
Saravanan S. Karuppagounder ◽  
Irina Gazaryan ◽  
John W. Cave ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Protein Stability ◽  
Oxygen Sensor ◽  
Lipid Peroxides ◽  
Prolyl Hydroxylase ◽  
Disease States ◽  
Hif Pathway ◽  
Hif Prolyl Hydroxylase ◽  
Kinetics Of

AbstractHypoxic adaptation mediated by HIF transcription factors has been shown to require mitochondria. Current models suggest that mitochondria regulate oxygen sensor (HIF prolyl hydroxylase) activity and HIF1α stability during hypoxia by either increasing mitochondrial peroxide as a second messenger or by serving as oxygen consumers that enhance the kinetics of cytoplasmic oxygen reduction. Here, we address the role of mitochondrial peroxide specifically in regulating HIF1α stability. We use state-of-the-art tools to evaluate the role of peroxide and other reactive oxygen species (ROS) in regulating HIF1α stability. We show that antioxidant enzymes are not homeostatically induced nor are peroxide levels increased in hypoxia. Forced expression of diverse antioxidant enzymes, all of which diminish peroxide, had disparate effects on HIF1α protein stability. Reduction of lipid peroxides by glutathione peroxidase-4 or superoxide by mitochondrial SOD failed to influence HIF1α protein stability. These data showed that mitochondrial, cytosolic and lipid ROS are dispensable for HIF1α stability and should affirm therapeutic efforts to activate the HIF pathway in disease states by HIF prolyl hydroxylase inhibition.

Role of intracellular antioxidant enzymes after in vivo myocardial ischemia and reperfusion

2003 ◽  
Vol 284 (1) ◽  
pp. H277-H282 ◽  
Author(s):  
Steven P. Jones ◽  
Michaela R. Hoffmeyer ◽  
Brent R. Sharp ◽  
Ye-Shih Ho ◽  
David J. Lefer
Keyword(s):  
Antioxidant Enzymes ◽  
Glutathione Peroxidase ◽  
Ischemia Reperfusion ◽  
Myocardial Necrosis ◽  
Myocardial Damage ◽  
Ischemia And Reperfusion ◽  
Myocardial Ischemia And Reperfusion

Reactive oxygen species induce myocardial damage after ischemia and reperfusion in experimental animal models. Numerous studies have investigated the deleterious effects of ischemia-reperfusion (I/R)-induced oxidant production using various pharmacological interventions. More recently, in vitro studies have incorporated gene-targeted mice to decipher the role of antioxidant enzymes in myocardial reperfusion injury. We examined the role of cellular antioxidant enzymes in the pathogenesis of myocardial I/R (MI/R) injury in vivo in gene-targeted mice. Neither deficiency nor overexpression of Cu-Zn superoxide dismutase (SOD) altered the extent of myocardial necrosis. Overexpression of glutathione peroxidase did not affect the degree of myocardial injury. Conversely, overexpression of manganese (Mn)SOD significantly attenuated myocardial necrosis after MI/R. Transthoracic echocardiography was performed on MnSOD-overexpressing and wild-type mice that were subjected to a more prolonged period of reperfusion. Cardiac output was significantly depressed in the nontransgenic but not the transgenic MnSOD-treated mice. Anterior wall motion was significantly impaired in the nontransgenic mice. These findings demonstrate an important role for MnSOD but not Cu/ZnSOD or glutathione peroxidase in mice after in vivo MI/R.

scholarly journals Extracellular Glutathione Peroxidase GPx3 and Its Role in Cancer

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2197 ◽  
Author(s):  
Caroline Chang ◽  
Beth L. Worley ◽  
Rébécca Phaëton ◽  
Nadine Hempel
Keyword(s):  
Antioxidant Enzymes ◽  
Glutathione Peroxidase ◽  
Cancer Progression ◽  
Mammalian Cells ◽  
Lipid Hydroperoxides ◽  
Therapeutic Approaches ◽  
Antioxidant Enzyme System ◽  
Disease Associations ◽  
Tumor Types

Mammalian cells possess a multifaceted antioxidant enzyme system, which includes superoxide dismutases, catalase, the peroxiredoxin/thioredoxin and the glutathione peroxidase systems. The dichotomous role of reactive oxygen species and antioxidant enzymes in tumorigenesis and cancer progression complicates the use of small molecule antioxidants, pro-oxidants, and targeting of antioxidant enzymes as therapeutic approaches for cancer treatment. It also highlights the need for additional studies to investigate the role and regulation of these antioxidant enzymes in cancer. The focus of this review is on glutathione peroxidase 3 (GPx3), a selenoprotein, and the only extracellular GPx of a family of oxidoreductases that catalyze the detoxification of hydro- and soluble lipid hydroperoxides by reduced glutathione. In addition to summarizing the biochemical function, regulation, and disease associations of GPx3, we specifically discuss the role and regulation of systemic and tumor cell expressed GPx3 in cancer. From this it is evident that GPx3 has a dichotomous role in different tumor types, acting as both a tumor suppressor and pro-survival protein. Further studies are needed to examine how loss or gain of GPx3 specifically affects oxidant scavenging and redox signaling in the extracellular tumor microenvironment, and how GPx3 might be targeted for therapeutic intervention.

scholarly journals The metabolic profile in laying hens of the Rosso race after 180 days of feed supplement with organic selenium

2016 ◽  
Vol 73 (2) ◽  
pp. 285
Author(s):  
Adrian Raduta ◽  
Dumitru Curca
Keyword(s):  
Superoxide Dismutase ◽  
Antioxidant Enzymes ◽  
Glutathione Peroxidase ◽  
Biochemical Markers ◽  
Metabolic Profile ◽  
Feed Supplement ◽  
Organic Selenium ◽  
Calcium Magnesium ◽  
Experimental Group

Selenium is a trace mineral with antioxidant proprieties, which, by mediating  the glutathione, indirectly protects the hemoglobin against the risk of oxidation by peroxides through three antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalaseThe experiment was done on 20 laying chicks from the Rosso race, 6 weeks old at the start. The chicks were divided in 2 batches, and one of the batches received feed enriched with organic selenium (Sel-Plex). After 180 days, biological samples were colected by cubital vein puncture and hematological and biochemical determinations were made. The results were tabled, graphically represented and biostatistically interpreted. In the experimental batch significant growths were observed in the erythrocyte constants: erithremie, hemoglobinemy, hematocrite and MCH. Of the biochemical markers significant growths were observed in: ascorbinemic acid, alkalin phospahasis and selenium. The following parameters dropped significantly : proteinemia, amylase and MCV. Changes were also observed in cholesterol, calcium, magnesium and other parameters, but without statisticaly value. In the present paper we have shown the beneficial role of organic selenium on some haematological and biochemical markers, resulting in a growth of erythropoiesis, and at the same time a intensification of the metabolic processes in the experimental group.

scholarly journals Catalytic Antioxidants in the Kidney

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 130
Author(s):  
Yu Ah Hong ◽  
Cheol Whee Park
Keyword(s):  
Antioxidant Enzymes ◽  
Reactive Nitrogen Species ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Lipid Peroxides ◽  
Hypertensive Nephropathy ◽  
Antioxidant Agents

Reactive oxygen species and reactive nitrogen species are highly implicated in kidney injuries that include acute kidney injury, chronic kidney disease, hypertensive nephropathy, and diabetic nephropathy. Therefore, antioxidant agents are promising therapeutic strategies for kidney diseases. Catalytic antioxidants are defined as small molecular mimics of antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, and some of them function as potent detoxifiers of lipid peroxides and peroxynitrite. Several catalytic antioxidants have been demonstrated to be effective in a variety of in vitro and in vivo disease models that are associated with oxidative stress, including kidney diseases. This review summarizes the evidence for the role of antioxidant enzymes in kidney diseases, the classifications of catalytic antioxidants, and their current applications to kidney diseases.

The role of Forkhead Box O 3a (FoxO3a) Transcription Factors in the Pathogenesis of Pulmonary Fibrosis

Pneumologie ◽  
2012 ◽  
Vol 66 (06) ◽  
Author(s):  
HM Al-Tamari ◽  
M Eschenhagen ◽  
A Schmall ◽  
R Savai ◽  
HA Ghofrani ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Pulmonary Fibrosis ◽  
Forkhead Box

Association of genetic polymorphism of cytokines and antioxidant enzymes with the development of asbestosis

2020 ◽  
Vol 60 (12) ◽  
pp. 898-903
Author(s):  
Lyudmila P. Kuzmina ◽  
Anastasiya G. Khotuleva ◽  
Evgeniy V. Kovalevsky ◽  
Nikolay N. Anokhin ◽  
Iraklij M. Tskhomariya
Keyword(s):  
Antioxidant Enzymes ◽  
Genetic Polymorphism ◽  
Genetic Predisposition ◽  
Risk Groups ◽  
Dust Exposure ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Gstp1 Gene ◽  
Polymorphic Variants

Introduction. Various industries widely use chrysotile asbestos, which determines the relevance of research aimed at the prevention of asbestos-related diseases. It is promising to assess the role of specific genes, which products are potentially involved in the development and regulation of certain links in the pathogenesis of asbestosis, forming a genetic predisposition to the disease. The study aims to analyze the presence of associations of genetic polymorphism of cytokines and antioxidant enzymes with asbestosis development. Materials and methods. Groups were formed for examination among employees of OJSC "Uralasbest" with an established diagnosis of asbestosis and without lung diseases. For each person included in the study, dust exposure doses were calculated considering the percentage of time spent at the workplace during the shift for the entire work time. Genotyping of single nucleotide polymorphisms of cytokines IL1b (rs16944), IL4 (rs2243250), IL6 (rs1800795), TNFα (rs1800629) and antioxidant enzymes SOD2 (rs4880), GSTP1 (rs1610011), CAT (rs1001179) was carried out. Results. The authors revealed the associations of polymorphic variants A511G IL1b gene (OR=2.457, 95% CI=1.232-4.899) and C47T SOD2 gene (OR=1.705, 95% CI=1.055-2.756) with the development of asbestosis. There was an increase in the T allele IL4 gene (C589T) frequency in persons with asbestosis at lower values of dust exposure doses (OR=2.185, 95% CI=1.057-4.514). The study showed the associations of polymorphism C589T IL4 gene and C174G IL6 gene with more severe asbestosis, polymorphism A313G GSTP1 gene with pleural lesions in asbestosis. Conclusion. Polymorphic variants of the genes of cytokines and antioxidant enzymes, the protein products directly involved in the pathogenetic mechanisms of the formation of asbestosis, contribute to forming a genetic predisposition to the development and severe course of asbestosis. Using the identified genetic markers to identify risk groups for the development and intense period of asbestos-related pathology will optimize treatment and preventive measures, considering the organism's characteristics.

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