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      Hydrogen Sulfide in Physiology and Pathogenesis of Bacteria and Viruses

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          Summary

          An increasing number of studies have established hydrogen sulfide (H 2S) gas as a major cytoprotectant and redox modulator. Following its discovery, H 2S has been found to have pleiotropic effects on physiology and human health. H 2S acts as a gasotransmitter and exerts its influence on gastrointestinal, neuronal, cardiovascular, respiratory, renal, and hepatic systems. Recent discoveries have clearly indicated the importance of H 2S in regulating vasorelaxation, angiogenesis, apoptosis, ageing, and metabolism. Contrary to studies in higher organisms, the role of H 2S in the pathophysiology of infectious agents such as bacteria and viruses has been less studied. Bacterial and viral infections are often accompanied by changes in the redox physiology of both the host and the pathogen. Emerging studies indicate that bacterial-derived H 2S constitutes a defense system against antibiotics and oxidative stress. The H 2S signaling pathway also seems to interfere with redox-based events affected on infection with viruses. This review aims to summarize recent advances on the emerging role of H 2S gas in the bacterial physiology and viral infections. Such studies have opened up new research avenues exploiting H 2S as a potential therapeutic intervention.

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          A common mechanism of cellular death induced by bactericidal antibiotics.

          Antibiotic mode-of-action classification is based upon drug-target interaction and whether the resultant inhibition of cellular function is lethal to bacteria. Here we show that the three major classes of bactericidal antibiotics, regardless of drug-target interaction, stimulate the production of highly deleterious hydroxyl radicals in Gram-negative and Gram-positive bacteria, which ultimately contribute to cell death. We also show, in contrast, that bacteriostatic drugs do not produce hydroxyl radicals. We demonstrate that the mechanism of hydroxyl radical formation induced by bactericidal antibiotics is the end product of an oxidative damage cellular death pathway involving the tricarboxylic acid cycle, a transient depletion of NADH, destabilization of iron-sulfur clusters, and stimulation of the Fenton reaction. Our results suggest that all three major classes of bactericidal drugs can be potentiated by targeting bacterial systems that remediate hydroxyl radical damage, including proteins involved in triggering the DNA damage response, e.g., RecA.
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            Two's company, three's a crowd: can H2S be the third endogenous gaseous transmitter?

            Rui Wang (2002)
            Bearing the public image of a deadly "gas of rotten eggs," hydrogen sulfide (H2S) can be generated in many types of mammalian cells. Functionally, H2S has been implicated in the induction of hippocampal long-term potentiation, brain development, and blood pressure regulation. By acting specifically on KATP channels, H2S can hyperpolarize cell membranes, relax smooth muscle cells, or decrease neuronal excitability. The endogenous metabolism and physiological functions of H2S position this gas well in the novel family of endogenous gaseous transmitters, termed "gasotransmitters." It is hypothesized that H2S is the third endogenous signaling gasotransmitter, besides nitric oxide and carbon monoxide. This positioning of H2S will open an exciting field-H2S physiology-encompassing realization of the interaction of H2S and other gasotransmitters, sulfurating modification of proteins, and the functional role of H2S in multiple systems. It may shed light on the pathogenesis of many diseases related to the abnormal metabolism of H2S.
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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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                Author and article information

                Journal
                100888706
                21614
                IUBMB Life
                IUBMB Life
                IUBMB life
                1521-6543
                1521-6551
                28 June 2018
                30 March 2018
                May 2018
                03 July 2018
                : 70
                : 5
                : 393-410
                Affiliations
                Department of Microbiology and Cell Biology, Centre for Infectious Disease Research, Indian Institute of Science (IISc), Bangalore, India
                Author notes
                [* ]Address correspondence to: Amit Singh, PhD., Assistant Professor, Department of Microbiology and Cell Biology, Centre for Infectious Disease Research, Indian Institute of Science (IISc), CV Raman Avenue, Bangalore 560012, India. Tel: 918022932604. Fax: 91-80-23602697. asingh@ 123456iisc.ac.in
                Article
                EMS78422
                10.1002/iub.1740
                6029659
                29601123
                eeccb3aa-f02b-4c7a-a7ec-e4e99b9c97ff

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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                hydrogen sulfide,cytoprotectant,antioxidant,metabolism,infection,mycobacterium tuberculosis,hiv

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