Hydrogen sulfide-based therapeutics: exploiting a unique but ubiquitous gasotransmitter

Nature Reviews Drug Discovery, Journal Year: 2015, Volume and Issue: 14(5), P. 329 - 345

Published: April 7, 2015

Language: Английский

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Placental Origins of Chronic Disease

Physiological Reviews, Journal Year: 2016, Volume and Issue: 96(4), P. 1509 - 1565

Published: Sept. 8, 2016

Epidemiological evidence links an individual's susceptibility to chronic disease in adult life events during their intrauterine phase of development. Biologically this should not be unexpected, for organ systems are at most plastic when progenitor cells proliferating and differentiating. Influences operating time can permanently affect structure functional capacity, the activity enzyme endocrine axes. It is now appreciated that such effects lay foundations a diverse array diseases become manifest many years later, often response secondary environmental stressors. Fetal development underpinned by placenta, forms interface between fetus its mother. All nutrients oxygen reaching must pass through organ. The placenta also has major functions, orchestrating maternal adaptations pregnancy mobilizing resources fetal use. In addition, it acts as selective barrier, creating protective milieu minimizing exposure hormones, glucocorticoids, xenobiotics, pathogens, parasites. shows remarkable capacity adapt adverse cues lessen impact on fetus. However, if placental function impaired, or exceeded, then may compromised. Here, we explore complex relationships phenotype developmental programming offspring. Ensuring optimal placentation offers new approach prevention disorders cardiovascular disease, diabetes, obesity, which epidemic proportions.

Language: Английский

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Regulation of mitochondrial bioenergetic function by hydrogen sulfide. Part I. Biochemical and physiological mechanisms

British Journal of Pharmacology, Journal Year: 2013, Volume and Issue: 171(8), P. 2099 - 2122

Published: Sept. 2, 2013

Until recently, hydrogen sulfide ( H 2 S ) was exclusively viewed a toxic gas and an environmental hazard, with its toxicity primarily attributed to the inhibition of mitochondrial C omplex IV , resulting in shutdown electron transport cellular ATP generation. Work over last decade established multiple biological regulatory roles as endogenous gaseous transmitter. is produced by cystathionine γ‐lyase CSE ), β‐synthase CBS 3‐mercaptopyruvate sulfurtransferase (3‐ MST ). In striking contrast inhibitory effect on recent studies showed that at lower concentrations, serves stimulator mammalian cells, acting donor. Endogenous mitochondrially localized 3‐ supports basal, physiological bioenergetic functions; activity this metabolic support declines aging. specialized conditions (calcium overload vascular smooth muscle, colon cancer cells), can also associate mitochondria; these enzymes, bioenergetics. The current article overviews biochemical mechanisms underlying stimulatory effects function bioenergetics discusses implication processes for normal physiology. relevance biology discussed context colonic epithelial cell physiology: colonocytes are exposed high levels enteric bacteria, serve barrier limit their entry into host, while, same time, utilizing it ‘fuel’. Linked Articles This part themed issue Mitochondrial Pharmacology: Energy, Injury & Beyond. To view other articles visit http://dx.doi.org/10.1111/bph.2014.171.issue‐8

Language: Английский

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Chemical foundations of hydrogen sulfide biology

Nitric Oxide, Journal Year: 2013, Volume and Issue: 35, P. 21 - 34

Published: July 9, 2013

Following nitric oxide (nitrogen monoxide) and carbon monoxide, hydrogen sulfide (or its newer systematic name sulfane, H2S) became the third small molecule that can be both toxic beneficial depending on concentration. In spite of impressive therapeutic potential, underlying mechanisms for effects remain unclear. Any novel mechanism has to obey fundamental chemical principles. H2S chemistry was studied long before biological relevance discovered, however, with a few exceptions, these past works have received relatively little attention in path exploring mechanistic conundrum functions. This review calls basic physical properties H2S, focuses between three potential targets: oxidants, metals thiol derivatives, discusses applications basics into biology methodology, introduces standard terminology this youthful field.

Language: Английский

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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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Key bioactive reaction products of the NO/H₂S interaction are S/N-hybrid species, polysulfides, and nitroxyl

Proceedings of the National Academy of Sciences, Journal Year: 2015, Volume and Issue: 112(34)

Published: July 29, 2015

Experimental evidence suggests that nitric oxide (NO) and hydrogen sulfide (H2S) signaling pathways are intimately intertwined, with mutual attenuation or potentiation of biological responses in the cardiovascular system elsewhere. The chemical basis this interaction is elusive. Moreover, polysulfides recently emerged as potential mediators H2S/sulfide signaling, but their biosynthesis relationship to NO remain enigmatic. We sought characterize nature, biology, bioactivity key reaction products formed NO/sulfide system. At physiological pH, we find form a network cascading reactions generate radical intermediates well anionic uncharged solutes, accumulation three major products: nitrosopersulfide (SSNO(-)), polysulfides, dinitrososulfite [N-nitrosohydroxylamine-N-sulfonate (SULFI/NO)], each distinct biology vitro vivo bioactivity. SSNO(-) resistant thiols cyanolysis, efficiently donates both sulfane sulfur NO, potently lowers blood pressure. Polysulfides synthesis/decomposition, they also decrease pressure enhance arterial compliance. SULFI/NO weak combined NO/nitroxyl donor releases mainly N2O on decomposition; although it affects only mildly, markedly increases cardiac contractility, formation its precursor sulfite likely contributes scavenging. Our results unveil an unexpectedly rich coupled between H2S/sulfide, suggesting either transmitter governed by concomitant S/N-hybrid species. This conceptual framework would seem offer ample opportunities for modulation fundamental processes redox switching trafficking.

Language: Английский

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The Role of Hydrogen Sulfide in Evolution and the Evolution of Hydrogen Sulfide in Metabolism and Signaling

Physiology, Journal Year: 2015, Volume and Issue: 31(1), P. 60 - 72

Published: Dec. 17, 2015

The chemical versatility of sulfur and its abundance in the prebiotic Earth as reduced sulfide (H 2 S) implicate this molecule origin life 3.8 billion years ago also a major source energy first seven-eighths evolution. tremendous increase ambient oxygen ∼600 million brought an end to H S source, S-dependent animals either became extinct, retreated isolated niches, or adapted. 3 molecular tinkering were not lost, however, much biochemical armamentarium easily adapted oxic environment where it contributes metabolism signaling even humans. This review examines role evolution signaling.

Language: Английский

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Hydrogen sulfide: An endogenous regulator of the immune system

Pharmacological Research, Journal Year: 2020, Volume and Issue: 161, P. 105119 - 105119

Published: Aug. 8, 2020

Hydrogen sulfide (H2S) is now recognized as an endogenous signaling gasotransmitter in mammals. It produced by mammalian cells and tissues various enzymes - predominantly cystathionine β-synthase (CBS), γ-lyase (CSE) 3-mercaptopyruvate sulfurtransferase (3-MST) but part of the H2S intestinal microbiota (colonic H2S-producing bacteria). Here we summarize available information on production functional role cell types typically associated with innate immunity (neutrophils, macrophages, dendritic cells, natural killer mast basophils, eosinophils) adaptive (T B lymphocytes) under normal conditions it relates to development inflammatory immune diseases. Special attention paid physiological pathophysiological aspects oral cavity colon, where parenchymal are exposed a special "H2S environment" due bacterial production. has many cellular molecular targets. Immune "surrounded" "cloud" H2S, result exogenous from surrounding which, turn, importantly regulates their viability function. Downregulation producing diseases, or genetic defects biosynthetic enzyme systems either lead spontaneous autoimmune disease accelerate onset worsen severity immune-mediated diseases (e.g. rheumatoid arthritis asthma). Low, regulated amounts when therapeutically delivered small molecule donors, improve function protect them against dysfunction induced noxious stimuli reactive oxygen species oxidized LDL). These effects contribute maintenance functions, can stimulate antimicrobial defenses exert anti-inflammatory therapeutic

Language: Английский

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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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Hydrogen sulfide in cancer: Friend or foe?

Nitric Oxide, Journal Year: 2015, Volume and Issue: 50, P. 38 - 45

Published: Aug. 20, 2015

Language: Английский

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