Effects of hydrogen sulfide on mitochondrial function and cellular bioenergetics

Redox Biology, Journal Year: 2020, Volume and Issue: 38, P. 101772 - 101772

Published: Oct. 28, 2020

Hydrogen sulfide (H2S) was once considered to have only toxic properties, until it discovered be an endogenous signaling molecule. The effects of H2S are dose dependent, with lower concentrations being beneficial and higher concentrations, cytotoxic. This scenario is especially true for the on mitochondrial function, where gasotransmitter inhibit electron transport chain, stimulate bioenergetics in multiple ways. Here we review role function its cellular physiology.

Language: Английский

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Polysulfide-mediated sulfhydration of SIRT1 prevents diabetic nephropathy by suppressing phosphorylation and acetylation of p65 NF-κB and STAT3

Redox Biology, Journal Year: 2020, Volume and Issue: 38, P. 101813 - 101813

Published: Nov. 25, 2020

Diabetic kidney disease is known as a major cause of chronic and end stage renal disease. Polysulfides, class chemical agents with chain sulfur atoms, are found to confer protective effects in acute injury. However, whether polysulfide donor, sodium tetrasulfide (Na2S4), confers against diabetic nephropathy remains unclear. Our results showed that Na2S4 treatment ameliorated dysfunctional histological damage kidneys through inhibiting the overproduction inflammation cytokine reactive oxygen species (ROS), well attenuating fibrosis cell apoptosis. Additionally, upregulated phosphorylation acetylation levels p65 nuclear factor κB (p65 NF-κB) signal transducer activator transcription 3 (STAT3) were abrogated by sirtuin-1 (SIRT1)-dependent manner. In tubular epithelial cells, directly sulfhydrated SIRT1 at two conserved CXXC domains (Cys371/374; Cys395/398), then induced dephosphorylation deacetylation its targeted proteins including NF-κB STAT3, thereby reducing high glucose (HG)-caused oxidative stress, apoptosis, response epithelial-to-mesenchymal transition (EMT) progression. Most importantly, inactivation specific inhibitor EX-527, small interfering RNA (siRNA), de-sulfhydration reagent dithiothreitol (DTT), or mutation Cys371/374 Cys395/398 sites abolished on insulting. These reveal polysulfides may attenuate lesions via STAT3 phosphorylation/acetylation sulfhydrating SIRT1.

Language: Английский

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Cysteine-derived hydrogen sulfide and gut health

Current Opinion in Clinical Nutrition & Metabolic Care, Journal Year: 2018, Volume and Issue: 22(1), P. 68 - 75

Published: Nov. 17, 2018

Hydrogen sulfide (H2S) is produced in the gut from cysteine by epithelial cells and intestinal microbiota. Initially considered as a toxic gas, pleiotropic effects of H2S are now recognized, especially colonic mucosa. The aim this review to present new experimental data indicating that cysteine-derived emerging key regulator health.Cysteine degradation microbiota emerged dominant pathway for production. Among bacteria producing cysteine, Fusobacterium appears pivotal genus associated with digestive diseases. promotes or alleviates mucosal inflammation, mostly according its high (high micromolar millimolar) low (nanomolar micromolar) concentration, respectively. maintains integrity mucus layer when derived endogenous metabolism but detrimental parameter excess microbes. In inflammatory bowel diseases, an upregulation production observed concomitantly downregulation enzymes implicated detoxification. colorectal cancer patients, both microbial at tumor site might contribute disease progression.H2S double-edge sword epithelium. This related bell-shaped H2S, protective effect concentration deleterious higher concentrations. As produces much more than metabolism, we consider bacterial source major determinant health.

Language: Английский

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Role of Hydrogen Sulfide in NRF2- and Sirtuin-Dependent Maintenance of Cellular Redox Balance

Antioxidants, Journal Year: 2018, Volume and Issue: 7(10), P. 129 - 129

Published: Sept. 28, 2018

Hydrogen sulfide (H₂S) has arisen as a critical gasotransmitter signaling molecule modulating cellular biological events related to health and diseases in heart, brain, liver, vascular systems immune response. Three enzymes mediate the endogenous production of H₂S: cystathione β-synthase (CBS), γ-lyase (CSE) 3-mercaptopyruvate sulfurtransferase (3-MST). CBS CSE localizations are organ-specific. 3-MST is mitochondrial cytosolic enzyme. The generation H₂S firmly regulated by these under normal physiological conditions. Recent studies have highlighted role redox homeostasis, it displays significant antioxidant properties. exerts effects through several mechanisms, such quenching reactive oxygen species (ROS) nitrogen (RNS), levels glutathione (GSH) thioredoxin (Trx-1) or increasing expression (AOE), activating transcription factor nuclear (erythroid-derived 2)-like 2 (NRF2). also influences activity histone deacetylase protein family sirtuins, which plays an important inhibiting oxidative stress cardiomyocytes during aging process AOE gene expression. This review focuses on NRF2 sirtuin pathways they homeostasis.

Language: Английский

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Signaling by hydrogen sulfide and cyanide through post-translational modification

Journal of Experimental Botany, Journal Year: 2019, Volume and Issue: 70(16), P. 4251 - 4265

Published: May 13, 2019

Abstract Two cysteine metabolism-related molecules, hydrogen sulfide and cyanide, which are considered toxic, have now been as signaling molecules. Hydrogen is produced in chloroplasts through the activity of sulfite reductase cytosol mitochondria by action sulfide-generating enzymes, regulates/affects essential plant processes such adaptation, development, photosynthesis, autophagy, stomatal movement, where interplay with other molecules occurs. The mechanism sulfide, modifies protein thiols to form persulfides, related its chemical features. This post-translational modification, called persulfidation, could play a protective role for against oxidative damage. cyanide during biosynthesis ethylene camalexin non-cyanogenic plants, detoxified sulfur-related enzymes. Cyanide functions include breaking seed dormancy, modifying responses biotic stress, inhibition root hair elongation. mode under investigation, although it has recently demonstrated perform modification thiocyanate, process S-cyanylation. Therefore, roles most probably performed specific residues, altering functions.

Language: Английский

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Hydrogen sulfide and vascular regulation – An update

Journal of Advanced Research, Journal Year: 2020, Volume and Issue: 27, P. 85 - 97

Published: May 16, 2020

Hydrogen sulfide (H2S) is considered to be the third gasotransmitter after carbon monoxide (CO) and nitric oxide (NO). It plays an important role in regulation of vascular homeostasis. Vascular remodeling have has proved related impaired H2S generation. This study aimed summarize discuss current data about function physiology pathophysiology as well underlying mechanisms. Endogenous hydrogen a primarily generated by enzymatic pathways regulated several metabolic pathways. physiologic regulator, inhibits proliferation, regulates its apoptosis autophagy cells controls tone. Accumulating evidence shows that downregulation pathway involved pathogenesis variety diseases, such hypertension, atherosclerosis pulmonary hypertension. Alternatively, supplementation may greatly help prevent progression diseases regulating tone, inhibiting inflammation, protecting against oxidative stress modulating cell apoptosis, which been verified animal experiments even clinical investigation. Besides, system angiotensin-converting enzyme (ACE) inhibitors play vital alleviating ischemic heart disease left ventricular dysfunction. Notably, sulfhydryl-containing ACEI inhibitor zofenopril superior other ACE due capability releasing, addition inhibition. The design application novel donors significant implications treatment vascular-related diseases. However, further research regarding required.

Language: Английский

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Nano-decocted ferrous polysulfide coordinates ferroptosis-like death in bacteria for anti-infection therapy

Nano Today, Journal Year: 2020, Volume and Issue: 35, P. 100981 - 100981

Published: Oct. 14, 2020

Antibacterial nanomaterials provide promising alternative strategies to combat the global challenge of bacterial infection due deteriorating resistance. However, few have been applied for intracellular bacteria killing or in vivo therapy potential cytotoxicity and poor biocompatibility. Here we present a strategy generate formula suitable anti-infective by decocting antibacterial nanomaterial. An aqueous containing ferrous iron polysulfide (Fe(II)Snaq) is prepared decoction procedure using nano-iron sulfide (nFeS) as raw substance. Theoretical calculation indicated that replacement sulfur atom an oxygen occurred, resulting release dissolution. The Fe(II)Snaq decocted from nFeS induced death with ferroptosis-like hallmarks, including enrichment, lipid peroxidation, glutathione (GSH) depletion. action was dependent on iron, which could be inhibited chelators, ferroptosis inhibitors, GSH, while prevented oxidation counteracted GSH. Furthermore, not only killed up 99 % planktonic within 5 min, but also suppressed 90 Staphylococcus aureus without triggering host cell. Administration achieved equivalent therapeutic effect vancomycin infectious pneumonia treatment significantly prolonged survival period septic mice. These results indicate can induce ferroptosis- like may formulated anti-infection therapy.

Language: Английский

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Potential role of the 3-mercaptopyruvate sulfurtransferase (3-MST)—hydrogen sulfide (H2S) pathway in cancer cells

Pharmacological Research, Journal Year: 2018, Volume and Issue: 154, P. 104083 - 104083

Published: Nov. 27, 2018

Language: Английский

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Advances and Opportunities in H₂S Measurement in Chemical Biology

JACS Au, Journal Year: 2023, Volume and Issue: 3(10), P. 2677 - 2691

Published: Sept. 21, 2023

Hydrogen sulfide (H

Language: Английский

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Contribution of NRF2 to sulfur metabolism and mitochondrial activity

Redox Biology, Journal Year: 2023, Volume and Issue: 60, P. 102624 - 102624

Published: Feb. 2, 2023

NF-E2-related factor 2 (NRF2) plays a crucial role in the maintenance of cellular homeostasis by regulating various enzymes and proteins that are involved redox reactions utilizing sulfur. While substantial impacts NRF2 on mitochondrial activity have been described, precise mechanism which regulates function is still not fully understood. Here, we demonstrated increased intracellular persulfides upregulating cystine transporter xCT encoded Slc7a11, well-known target gene. Persulfides shown to play an important function. Supplementation with glutathione trisulfide (GSSSG), form persulfide, elevated membrane potential (MMP), oxygen consumption rate (OCR) promoted ATP production. Persulfide-mediated activation was require sulfur oxidation pathway, especially sulfide quinone oxidoreductase (SQOR). Consistently, NRF2-mediated also dependent SQOR activity. This study clarified facilitation persulfide production metabolism mitochondria increasing cysteine availability one mechanisms for NRF2-dependent activation.

Language: Английский

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