Endogenous Hydrogen Sulfide Production Is Essential for Dietary Restriction Benefits

Cell, Journal Year: 2014, Volume and Issue: 160(1-2), P. 132 - 144

Published: Dec. 23, 2014

Language: Английский

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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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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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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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A timeline of hydrogen sulfide (H2S) research: From environmental toxin to biological mediator

Biochemical Pharmacology, Journal Year: 2017, Volume and Issue: 149, P. 5 - 19

Published: Sept. 23, 2017

Language: Английский

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Amino acid metabolism in intestinal bacteria and its potential implications for mammalian reproduction

Molecular Human Reproduction, Journal Year: 2015, Volume and Issue: 21(5), P. 389 - 409

Published: Jan. 20, 2015

Reproduction is vital for producing offspring and preserving genetic resources. However, incidences of many reproductive disorders (e.g. miscarriage, intrauterine growth restriction, premature delivery lower sperm quality) have either increased dramatically or remained at high rates over the last decades. Mounting evidence shows a strong correlation between enteral protein nutrition reproduction. Besides serving as major nutrients in diet, amino acids (AA) are signaling molecules regulation diverse physiological processes, ranging from spermatogenesis to oocyte fertilization embryo implantation. Notably, numbers bacteria intestine exceed host cells by 10 times. Microbes small-intestinal lumen actively metabolize large amounts dietary AA and, therefore, affect entry into portal circulation whole-body utilization. Changes composition abundance AA-metabolizing gut during pregnancy, well their translocation uterus, may alter uterine function epigenetic modifications maternal physiology metabolism, which crucial pregnancy recognition fetal development. Thus, presence microbiota metabolites environments endometrium placenta) breast milk likely unique signature programming microbiome metabolism both fetus infant. Dietary intervention with functional AA, probiotics prebiotics activity intestinal ameliorate prevent development metabolic syndrome, while improving performance males females offspring.

Language: Английский

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Non-enzymatic hydrogen sulfide production from cysteine in blood is catalyzed by iron and vitamin B6

Communications Biology, Journal Year: 2019, Volume and Issue: 2(1)

Published: May 21, 2019

Abstract Hydrogen sulfide (H 2 S) plays important roles in metabolism and health. Its enzymatic generation from sulfur-containing amino acids (SAAs) is well characterized. However, the existence of non-enzymatic H S production SAAs, chemical mechanism, its biological implications remain unclear. Here we present vitro blood via a reaction specific for SAA cysteine serving as substrate requires coordinated catalysis by Vitamin B 6 , pyridoxal(phosphate), iron under physiological conditions. An initial cysteine-aldimine formed nucleophilic attack group to pyridoxal(phosphate) aldehyde group. Free or heme-bound drives formation cysteine-quinonoid, thiol elimination, hydrolysis desulfurated aldimine back pyridoxal(phosphate). The ultimately produces pyruvate, NH 3 S. This work highlights inducible robust select tissues, whereas iron-catalyzed contributes underappreciated basal systemically with pathophysiological hemolytic, overload, hemorrhagic disorders.

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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Implications of hydrogen sulfide in colorectal cancer: Mechanistic insights and diagnostic and therapeutic strategies

Redox Biology, Journal Year: 2023, Volume and Issue: 59, P. 102601 - 102601

Published: Jan. 7, 2023

Hydrogen sulfide (H2S) is an important signaling molecule in colorectal cancer (CRC). It produced the colon by catalytic synthesis of colonocytes' enzymatic systems and release intestinal microbes, oxidatively metabolized mitochondria. Both endogenous H2S colonic epithelial cells exogenous lumen contribute to onset progression CRC. The up-regulation synthetases thought be cause elevated levels CRC cells. Different diagnostic probes combination therapies, as well tumor treatment approaches through modulation, have been developed recent years become active area investigation for diagnosis In this review, we focus on specific mechanisms production oxidative metabolism function occurrence, progression, diagnosis, We also discuss present challenges provide insights into future research burgeoning field.

Language: Английский

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