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      Hydrogen Sulfide: From a Toxic Molecule to a Key Molecule of Cell Life

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          Abstract

          Hydrogen sulfide (H 2S) has always been considered toxic, but a huge number of articles published more recently showed the beneficial biochemical properties of its endogenous production throughout all regna. In this review, the participation of H 2S in many physiological and pathological processes in animals is described, and its importance as a signaling molecule in plant systems is underlined from an evolutionary point of view. H 2S quantification methods are summarized and persulfidation is described as the underlying mechanism of action in plants, animals and bacteria. This review aims to highlight the importance of its crosstalk with other signaling molecules and its fine regulation for the proper function of the cell and its survival.

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          Most cited references186

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          The vasorelaxant effect of H(2)S as a novel endogenous gaseous K(ATP) channel opener.

          Hydrogen sulfide (H(2)S) has been traditionally viewed as a toxic gas. It is also, however, endogenously generated from cysteine metabolism. We attempted to assess the physiological role of H(2)S in the regulation of vascular contractility, the modulation of H(2)S production in vascular tissues, and the underlying mechanisms. Intravenous bolus injection of H(2)S transiently decreased blood pressure of rats by 12- 30 mmHg, which was antagonized by prior blockade of K(ATP) channels. H(2)S relaxed rat aortic tissues in vitro in a K(ATP) channel-dependent manner. In isolated vascular smooth muscle cells (SMCs), H(2)S directly increased K(ATP) channel currents and hyperpolarized membrane. The expression of H(2)S-generating enzyme was identified in vascular SMCs, but not in endothelium. The endogenous production of H(2)S from different vascular tissues was also directly measured with the abundant level in the order of tail artery, aorta and mesenteric artery. Most importantly, H(2)S production from vascular tissues was enhanced by nitric oxide. Our results demonstrate that H(2)S is an important endogenous vasoactive factor and the first identified gaseous opener of K(ATP) channels in vascular SMCs.
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            H2S signals through protein S-sulfhydration.

            Hydrogen sulfide (H2S), a messenger molecule generated by cystathionine gamma-lyase, acts as a physiologic vasorelaxant. Mechanisms whereby H2S signals have been elusive. We now show that H2S physiologically modifies cysteines in a large number of proteins by S-sulfhydration. About 10 to 25% of many liver proteins, including actin, tubulin, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), are sulfhydrated under physiological conditions. Sulfhydration augments GAPDH activity and enhances actin polymerization. Sulfhydration thus appears to be a physiologic posttranslational modification for proteins.
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              Hydrogen sulfide is an endogenous stimulator of angiogenesis.

              The goal of the current study was to investigate the role of exogenous and endogenous hydrogen sulfide (H(2)S) on neovascularization and wound healing in vitro and in vivo. Incubation of endothelial cells (ECs) with H(2)S enhanced their angiogenic potential, evidenced by accelerated cell growth, migration, and capillary morphogenesis on Matrigel. Treatment of chicken chorioallantoic membranes (CAMS) with H(2)S increased vascular length. Exposure of ECs to H(2)S resulted in increased phosphorylation of Akt, ERK, and p38. The K(ATP) channel blocker glibenclamide or the p38 inhibitor SB203580 abolished H(2)S-induced EC motility. Since glibenclamide inhibited H(2)S-triggered p38 phosphorylation, we propose that K(ATP) channels lay upstream of p38 in this process. When CAMs were treated with H(2)S biosynthesis inhibitors dl-propylargylglycine or beta-cyano-L-alanine, a reduction in vessel length and branching was observed, indicating that H(2)S serves as an endogenous stimulator of the angiogenic response. Stimulation of ECs with vascular endothelial growth factor (VEGF) increased H(2)S release, while pharmacological inhibition of H(2)S production or K(ATP) channels or silencing of cystathionine gamma-lyase (CSE) attenuated VEGF signaling and migration of ECs. These results implicate endothelial H(2)S synthesis in the pro-angiogenic action of VEGF. Aortic rings isolated from CSE knockout mice exhibited markedly reduced microvessel formation in response to VEGF when compared to wild-type littermates. Finally, in vivo, topical administration of H(2)S enhanced wound healing in a rat model, while wound healing was delayed in CSE(-/-) mice. We conclude that endogenous and exogenous H(2)S stimulates EC-related angiogenic properties through a K(ATP) channel/MAPK pathway.
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                Author and article information

                Journal
                Antioxidants (Basel)
                Antioxidants (Basel)
                antioxidants
                Antioxidants
                MDPI
                2076-3921
                15 July 2020
                July 2020
                : 9
                : 7
                : 621
                Affiliations
                [1 ]Department of Genetics, Development and Cell Biology, Iowa State University, Ames, IA 50011, USA; bassham@ 123456iastate.edu
                [2 ]Institute of Plant Biochemistry and Photosynthesis, University of Seville and CSIC, 41092 Seville, Spain; gotor@ 123456ibvf.csic.es (C.G.); lromero@ 123456ibvf.csic.es (L.C.R.)
                Author notes
                [* ]Correspondence: aaroca@ 123456us.es
                Author information
                https://orcid.org/0000-0003-4915-170X
                https://orcid.org/0000-0003-4272-7446
                https://orcid.org/0000-0001-7411-9360
                Article
                antioxidants-09-00621
                10.3390/antiox9070621
                7402122
                32679888
                6134017c-d58f-475c-a492-48e0e253296d
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 02 June 2020
                : 13 July 2020
                Categories
                Review

                hydrogen sulfide,crosstalk,persulfidation,gasotransmitter,signaling molecules,human and plant therapies

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