International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

Pharmacological Reviews, Journal Year: 2017, Volume and Issue: 69(4), P. 497 - 564

Published: Oct. 1, 2017

Over the last decade, hydrogen sulfide (H₂S) has emerged as an important endogenous gasotransmitter in mammalian cells and tissues. Similar to previously characterized gasotransmitters nitric oxide carbon monoxide, H₂S is produced by various enzymatic reactions regulates a host of physiologic pathophysiological processes levels are decreased number conditions (e.g., diabetes mellitus, ischemia, aging) increased other states inflammation, critical illness, cancer). decades, multiple approaches have been identified for therapeutic exploitation H₂S, either based on donation or inhibition biosynthesis. can be achieved through inhalation gas and/or parenteral enteral administration so-called fast-releasing donors (salts such NaHS Na₂S) slow-releasing (GYY4137 being prototypical compound used hundreds studies vitro vivo). Recent work also identifies with regulated release profiles, including oxidant-triggered donors, pH-dependent esterase-activated organelle-targeted mitochondrial) compounds. There where existing, clinically approved drugs classes nonsteroidal anti-inflammatories) coupled H₂S-donating groups (the most advanced clinical trials ATB-346, derivative non-steroidal anti-inflammatory naproxen). For pharmacological synthesis, there now several small molecule compounds targeting each three H₂S-producing enzymes cystathionine-β-synthase (CBS), cystathionine-γ-lyase, 3-mercaptopyruvate sulfurtransferase. Although many these their limitations (potency, selectivity), molecules, especially combination genetic approaches, instrumental delineation biologic involving production. Moreover, some cell-permeable prodrugs CBS inhibitor aminooxyacetate, benserazide, potentially repurposable inhibitor) may serve starting points future translation. The present article overviews currently known biosynthesis inhibitors, delineates mode action, offers examples effects potential utility.

Language: Английский

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A Review of Hydrogen Sulfide Synthesis, Metabolism, and Measurement: Is Modulation of Hydrogen Sulfide a Novel Therapeutic for Cancer?

Antioxidants and Redox Signaling, Journal Year: 2018, Volume and Issue: 31(1), P. 1 - 38

Published: May 23, 2018

Hydrogen sulfide (H

Language: Английский

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Simple spectrophotometric assay for measuring catalase activity in biological tissues

BMC Biochemistry, Journal Year: 2018, Volume and Issue: 19(1)

Published: Aug. 3, 2018

The details of a precise, accurate, and sensitive spectrophotometric method for measuring catalase activity are presented here. assay was established biological samples depends on the rapid formation stable colored carbonato-cobaltate (III) complex. Samples exhibiting incubated with hydrogen peroxide solution 2 min prior to mixing incubation enzymatic reaction mixture cobalt-bicarbonate reagent, which assesses non-reacting peroxide. Catalase is always directly proportional rate dissociation Hydrogen acts oxidize cobalt (II) in presence bicarbonate ions; this process ends production complex ([Co (CO3)3]Co). formed end product has two maximum absorbance peaks: 440 nm 640 nm. 440-nm peak been utilized assessing activity. results current erythrocyte lysate homogenates were computationally identical those dichromate (r = 0.9950). coefficient variation calculated determine imprecision assay. within-run between-run 2.96 3.83%, respectively. This appropriate analyzing bacteria, red blood cells liver kidney tissue homogenates.

Language: Английский

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The role of polysulfide dianions and radical anions in the chemical, physical and biological sciences, including sulfur-based batteries

Chemical Society Reviews, Journal Year: 2019, Volume and Issue: 48(12), P. 3279 - 3319

Published: Jan. 1, 2019

Polysulfide dianions and radical anions play a crucial role in biological chemistry, geochemical processes, alkali metal–sulfur batteries, organic syntheses, coordination materials sciences.

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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The role of catalases in the prevention/promotion of oxidative stress

Journal of Inorganic Biochemistry, Journal Year: 2019, Volume and Issue: 197, P. 110699 - 110699

Published: April 26, 2019

Language: Английский

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Hydrogen Sulfide (H2S) and Polysulfide (H2Sn) Signaling: The First 25 Years

Biomolecules, Journal Year: 2021, Volume and Issue: 11(6), P. 896 - 896

Published: June 16, 2021

Since the first description of hydrogen sulfide (H2S) as a toxic gas in 1713 by Bernardino Ramazzini, most studies on H2S have concentrated its toxicity. In 1989, Warenycia et al. demonstrated existence endogenous brain, suggesting that may physiological roles. 1996, we is potential signaling molecule, which can be produced cystathionine β-synthase (CBS) to modify neurotransmission brain. Subsequently, showed relaxes vascular smooth muscle synergy with nitric oxide (NO) and γ-lyase (CSE) another producing enzyme. This study also opened up new research area crosstalk between NO. The cytoprotective effect, anti-inflammatory activity, energy formation, oxygen sensing been subsequently demonstrated. Two additional pathways for production 3-mercaptopyruvate sulfurtransferase (3MST) from l- d-cysteine identified. We discovered polysulfides (H2Sn, n ≥ 2) are molecules 3MST. H2Sn regulate activity ion channels enzymes, well even growth tumors. S-Sulfuration (S-sulfhydration) proposed Snyder main mechanism H2S/H2Sn underlying regulation target proteins. mini review focuses key findings during 25 years.

Language: Английский

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Metabolism of hydrogen sulfide (H2S) and Production of Reactive Sulfur Species (RSS) by superoxide dismutase

Redox Biology, Journal Year: 2017, Volume and Issue: 15, P. 74 - 85

Published: Nov. 21, 2017

Reactive sulfur species (RSS) such as H2S, HS•, H2Sn, (n = 2–7) and HS2•- are chemically similar to H2O the reactive oxygen (ROS) HO•, H2O2, O2•- act on common biological effectors. RSS were present in evolution long before ROS, because both metabolized by catalase it has been suggested that "antioxidant" enzymes originally evolved regulate may continue do so today. Here we examined metabolism Cu/Zn superoxide dismutase (SOD) using amperometric electrodes for dissolved a polysulfide-specific fluorescent probe (SSP4), mass spectrometry identify specific polysulfides (H2S2-H2S5). H2S was concentration- oxygen-dependently oxidized 1 μM SOD (mainly H2S2, lesser extent H2S3 H2S5) with an EC50 of approximately 380 H2S. concentrations > 750 inhibited oxidation (IC50 1.25 mM) complete inhibition when 1.75 mM. Polysulfides not SOD. preferred over hydrosulfide anion (HS-), whereas HS- polysulfide production. In hypoxia, other possible electron donors nitrate, nitrite, sulfite, sulfate, thiosulfate metabisulfite ineffective. Manganese also catalyzed form polysulfides, but did metabolize indicating attributes these SODs. These experiments suggest that, unlike well-known SOD-mediated dismutation two H2O2 O2, catalyzes reaction O2 persulfide. can then combine various ways oxides. It is (or polysulfides) interact/react cysteines affect catalytic activity or directly contribute sulfide metabolism. Our studies have ancient mechanism detoxify along contemporary organisms.

Language: Английский

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Hydrogen Sulfide Biochemistry and Interplay with Other Gaseous Mediators in Mammalian Physiology

Oxidative Medicine and Cellular Longevity, Journal Year: 2018, Volume and Issue: 2018(1)

Published: Jan. 1, 2018

Hydrogen sulfide (H 2 S) has emerged as a relevant signaling molecule in physiology, taking its seat bona fide gasotransmitter akin to nitric oxide (NO) and carbon monoxide (CO). After being merely regarded toxic poisonous molecule, it is now recognized that mammalian cells are equipped with sophisticated enzymatic systems for H S production breakdown. The role of mainly related ability modify different protein targets, particularly by promoting persulfidation cysteine residues interacting metal centers, mostly hemes. been shown regulate myriad cellular processes multiple physiological consequences. As such, dysfunctional metabolism increasingly implicated pathologies, from cardiovascular neurodegenerative diseases cancer. highly diffusible reactive species, the intra‐ extracellular levels have be kept under tight control and, accordingly, regulation occurs at levels. Interestingly, even though S, NO, CO similar modes action parallel regulatory targets or precisely because that, there increasing evidence crosstalk between three gasotransmitters. Herein reviewed biochemistry, metabolism, function hydrogen sulfide, well interplay other gasotransmitters, NO CO.

Language: Английский

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H2S and polysulfide metabolism: Conventional and unconventional pathways

Biochemical Pharmacology, Journal Year: 2017, Volume and Issue: 149, P. 77 - 90

Published: Dec. 14, 2017

Language: Английский

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