Hydrogen Sulfide, an Endogenous Stimulator of Mitochondrial Function in Cancer Cells DOI Creative Commons
Csaba Szabó

Cells, Journal Year: 2021, Volume and Issue: 10(2), P. 220 - 220

Published: Jan. 22, 2021

Hydrogen sulfide (H2S) has a long history as toxic gas and environmental hazard; inhibition of cytochrome c oxidase (mitochondrial Complex IV) is viewed primary mode its cytotoxic action. However, studies conducted over the last two decades unveiled multiple biological regulatory roles H2S an endogenously produced mammalian gaseous transmitter. Cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) 3-mercaptopyruvate sulfurtransferase (3-MST) are currently principal H2S-generating enzymes. In contrast to inhibitory (toxicological) mitochondrial effects, at lower (physiological) concentrations, serves stimulator electron transport in mitochondria, by acting donor—with sulfide:quinone oxidoreductase (SQR) being immediate acceptor. The significant various cancer cells, many which exhibit high expression partial localization producing addition stimulation ATP production, endogenous cells include maintenance organization (protection against fission) DNA repair (via assembly complexes). current article overviews state-of-the-art knowledge regarding functions cells.

Language: Английский

Physiological roles of hydrogen sulfide in mammalian cells, tissues, and organs DOI
Giuseppe Cirino, Csaba Szabó, Andreas Papapetropoulos

et al.

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

Citations

289
A timeline of hydrogen sulfide (H2S) research: From environmental toxin to biological mediator DOI
Csaba Szabó

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

Published: Sept. 23, 2017

Language: Английский

Citations

230
Hydrogen sulfide: An endogenous regulator of the immune system DOI Creative Commons
Nahzli Dilek, Andreas Papapetropoulos, Tracy Toliver‐Kinsky

et al.

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

Citations

227
Effects of hydrogen sulfide on mitochondrial function and cellular bioenergetics DOI Creative Commons
Bindu D. Paul, Solomon H. Snyder, Khosrow Kashfi

et al.

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

Citations

201
Pyruvate kinase M2 (PKM2) in cancer and cancer therapeutics DOI

Susi Zhu,

Yeye Guo, Xu Zhang

et al.

Cancer Letters, Journal Year: 2020, Volume and Issue: 503, P. 240 - 248

Published: Nov. 24, 2020

Language: Английский

Citations

164
Cystathionine-β-synthase: Molecular Regulation and Pharmacological Inhibition DOI Creative Commons
Karim Zuhra,

Fiona Augsburger,

Tomáš Majtan

et al.

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

Citations

162
NBD-based synthetic probes for sensing small molecules and proteins: design, sensing mechanisms and biological applications DOI
Chenyang Jiang, Haojie Huang,

Xueying Kang

et al.

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(13), P. 7436 - 7495

Published: Jan. 1, 2021

Compounds with a nitrobenzoxadiazole (NBD) skeleton exhibit high reactivity toward biological nucleophilies accompanied by distinct colorimetric and fluorescent changes, environmental sensitivity, small size, all of which facilitate biomolecular sensing self-assembly.

Language: Английский

Citations

148
Sulfide regulation of cardiovascular function in health and disease DOI Open Access
Gopi K. Kolluru, Rodney E. Shackelford, Xinggui Shen

et al.

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

Published: Aug. 5, 2022

Language: Английский

Citations

136
Capture of toxic gases in MOFs: SO2, H2S, NH3 and NOx DOI Creative Commons

Eva Martínez‐Ahumada,

Mariana L. Díaz‐Ramírez, Miriam De J. Velásquez-Hernández

et al.

Chemical Science, Journal Year: 2021, Volume and Issue: 12(20), P. 6772 - 6799

Published: Jan. 1, 2021

MOFs are promising candidates for the capture of toxic gases such as SO2, H2S, NH3 and NOx. Understanding role different chemical functionalities, within pores MOFs, is key accomplishing superior captures these gases.

Language: Английский

Citations

123
Intelligent polymeric hydrogen sulfide delivery systems for therapeutic applications DOI Creative Commons
Fan Rong, Tengjiao Wang, Qian Zhou

et al.

Bioactive Materials, Journal Year: 2022, Volume and Issue: 19, P. 198 - 216

Published: April 13, 2022

Hydrogen sulfide (H2S) plays an important role in regulating various pathological processes such as protecting mammalian cell from harmful injuries, promoting tissue regeneration, and the process of diseases caused by physiological disorders. Studies have revealed that effects H2S are highly associated with its concentrations. At relatively low concentration, shows beneficial functions. However, long-time high-dose donation would inhibit regular biological process, resulting dysfunction apoptosis. To regulate dosage delivery for precision medicine, systems intelligent characteristics were developed a variety biocompatibility polymers been utilized to establish polymeric systems, abilities specifically target lesions, smartly respond microenvironments, well real-timely monitor lesion conditions incorporating imaging-capable moieties. In this review, we focus on design, preparation, therapeutic applications cardiovascular therapy, inflammatory regenerative cancer therapy bacteria-associated therapy. Strategies precise therapies especially imaging-guided theranostics highlighted. Since donors stimuli-responsive characters vital components establishing development is also briefly introduced.

Language: Английский

Citations

70