Physiological roles of hydrogen sulfide in mammalian cells, tissues, and organs

Physiological Reviews, Journal Year: 2022, Volume and Issue: 103(1), P. 31 - 276

Published: April 18, 2022

Over the last two decades, hydrogen sulfide (H2S) has emerged as an endogenous regulator of a broad range physiological functions. H2S belongs to class molecules known gasotransmitters, which typically include nitric oxide (NO) and carbon monoxide (CO). Three enzymes are recognized sources in various cells tissues: cystathionine γ-lyase (CSE), β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MST). The present article reviews regulation these well pathways their enzymatic nonenzymatic degradation elimination. multiple interactions with other labile (e.g., NO) reactive oxygen species also outlined. Next, biological targets signaling outlined, special reference or oxidative posttranscriptional modification (persulfidation sulfhydration) proteins effect on channels intracellular second messenger pathways, gene transcription translation, cellular bioenergetics metabolism. pharmacological molecular tools currently available study physiology reviewed, including utility limitations. In subsequent sections, role functions is membrane potential, endo- exocytosis, cell organelles (endoplasmic reticulum, Golgi, mitochondria), movement, cycle, differentiation, aspects regulated death. roles types organ systems overviewed, red blood cells, immune central peripheral nervous (with focus neuronal transmission, learning, memory formation), vascular function (including angiogenesis its specialized cerebrovascular, renal, pulmonary beds) senses, vision, hearing, taste smell, pain-sensing. Finally, (lung, heart, liver, kidney, urogenital organs, reproductive system, bone cartilage, skeletal muscle, endocrine organs) presented, aging) but extending some common pathophysiological conditions. From data, wide array significant all emerges characteristic bell-shaped biphasic effects highlighted. addition, key aspects, debated areas, future research translational areas identified.

Language: Английский

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Hydrogen sulfide signaling in mitochondria and disease

The FASEB Journal, Journal Year: 2019, Volume and Issue: 33(12), P. 13098 - 13125

Published: Oct. 24, 2019

Hydrogen sulfide can signal through 3 distinct mechanisms: 1) reduction and/or direct binding of metalloprotein heme centers, 2) serving as a potent antioxidant reactive oxygen species/reactive nitrogen species scavenging, or 3) post‐translational modification proteins by addition thiol (‐SH) group onto cysteine residues: process known persulfidation. Below toxic levels, hydrogen promotes mitochondrial biogenesis and function, thereby conferring protection against cellular stress. For these reasons, increases in sulfide‐producing enzymes have been implicated several human disease states. This review will first summarize our current understanding production metabolism, well its signaling mechanisms; second, this work detail the mechanisms mitochondria implications mitochondrial‐specific impacts pathologic conditions.—Murphy, B., Bhattacharya, R., Mukherjee, P. disease. FASEB J. 33, 13098–13125 (2019). www.fasebj.org

Language: Английский

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Cystathionine-β-synthase: Molecular Regulation and Pharmacological Inhibition

Biomolecules, Journal Year: 2020, Volume and Issue: 10(5), P. 697 - 697

Published: April 30, 2020

Cystathionine-β-synthase (CBS), the first (and rate-limiting) enzyme in transsulfuration pathway, is an important mammalian health and disease. Its biochemical functions under physiological conditions include metabolism of homocysteine (a cytotoxic molecule cardiovascular risk factor) generation hydrogen sulfide (H2S), a gaseous biological mediator with multiple regulatory roles vascular, nervous, immune system. CBS up-regulated several diseases, including Down syndrome many forms cancer; these conditions, preclinical data indicate that inhibition or inactivation exerts beneficial effects. This article overviews current information on expression, tissue distribution, roles, biochemistry CBS, followed by comprehensive overview direct indirect approaches to inhibit enzyme. Among small-molecule inhibitors, review highlights specificity selectivity problems related commonly used “CBS inhibitors” (e.g., aminooxyacetic acid) provides their pharmacological actions various disease models.

Language: Английский

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Sulfide regulation of cardiovascular function in health and disease

Nature Reviews Cardiology, Journal Year: 2022, Volume and Issue: 20(2), P. 109 - 125

Published: Aug. 5, 2022

Language: Английский

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Activity-Based Fluorescent Probes for Hydrogen Sulfide and Related Reactive Sulfur Species

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(7), P. 4124 - 4257

Published: March 21, 2024

Hydrogen sulfide (H2S) is not only a well-established toxic gas but also an important small molecule bioregulator in all kingdoms of life. In contemporary biology, H2S often classified as "gasotransmitter," meaning that it endogenously produced membrane permeable carries out essential cellular processes. Fluorescent probes for and related reactive sulfur species (RSS) detection provide cornerstone investigating the multifaceted roles these molecules complex biological systems. A now common approach to develop such tools "activity-based probes" couple specific H2S-mediated chemical reaction fluorescent output. This Review covers different types highlights mechanisms by which each probe type activated RSS. Common examples include reduction oxidized nitrogen motifs, disulfide exchange, electrophilic reactions, metal precipitation, coordination. addition, we outline complementary activity-based imaging reductant-labile sulfane species, including persulfides polysulfides. For highlighted this Review, focus on systems with demonstrated compatibility or applications. Building from breadth reported strategies application, highlight key unmet challenges future opportunities advancing

Language: Английский

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Erythrocyte metabolism

Acta Physiologica, Journal Year: 2024, Volume and Issue: 240(3)

Published: Jan. 25, 2024

Abstract Our aim is to present an updated overview of the erythrocyte metabolism highlighting its richness and complexity. We have manually collected connected available biochemical pathways integrated them into a functional metabolic map. The focus this map on main consisting glycolysis, pentose phosphate pathway, redox metabolism, oxygen purine/nucleoside membrane transport. Other recently emerging are also curated, like methionine salvage glyoxalase system, carnitine lands cycle, as well remnants carboxylic acid metabolism. An additional goal review dynamics providing key numbers used perform basic quantitative analyses. By synthesizing experimental computational data, we conclude that foundations Additionally, can sense levels oxidative stress adjusting mechanics, function. In conclusion, fine‐tuning controls one most important biological processes, is, loading, transport, delivery.

Language: Английский

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Hydrogen sulfide (H2S) metabolism: Unraveling cellular regulation, disease implications, and therapeutic prospects for precision medicine

Nitric Oxide, Journal Year: 2024, Volume and Issue: 144, P. 20 - 28

Published: Jan. 17, 2024

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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Folic Acid Supplementation in Patients with Elevated Homocysteine Levels

Advances in Therapy, Journal Year: 2020, Volume and Issue: 37(10), P. 4149 - 4164

Published: Aug. 26, 2020

Folic acid is the most important dietary determinant of homocysteine (Hcy). Hcy serves as a critical intermediate in methylation reactions. It created from methionine and either converted back to or transformed into cysteine. This process aided through several enzymes three vitamins, folic acid, B12, B6. Daily supplementation with 0.5–5.0 mg typically lowers plasma levels by approximately 25%. Hyperhomocysteinemia known risk factor for coronary artery disease. In this regard, elevated have been found majority patients vascular A literature review various disease states including cardiovascular was conducted. article based on previously conducted studies does not contain any human participants animals performed authors. review, we discuss biochemistry biosynthesis, hydrogen sulfide bioavailability, pathogenesis hyperhomocysteinemia its role disease, treatment states. should be recommended patient who has an level, level measured treated at early age, since easily obtained may likely reduce other deleterious pathologic processes high-risk populations.

Language: Английский

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Anti‐inflammatory and antiviral roles of hydrogen sulfide: Rationale for considering H₂S donors in COVID‐19 therapy

British Journal of Pharmacology, Journal Year: 2020, Volume and Issue: 177(21), P. 4931 - 4941

Published: Aug. 12, 2020

The COVID-19 pandemic caused by SARS-Cov-2 demands rapid, safe and effective therapeutic options. In the last decades, endogenous gasotransmitter hydrogen sulfide (H

Language: Английский

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