Hydrogen sulfide (H2S) is a poisonous gas which can be lethal. However, it is also produced endogenously, thus belonging to the family of gasotransmitters along with nitric oxide and carbon monoxide. H2S is in fact involved in mediating several signaling and cytoprotective functions, for example in the nervous, cardiovascular, and gastrointestinal systems, such as neuronal transmission, blood pressure regulation and insulin release, among others. When increased, it can mediate inflammation and apoptosis, with a role in shock. When decreased, it can be involved in atherosclerosis, hypertension, myocardial infarction, diabetes, sexual dysfunction, and gastric ulcer; it notably interacts with the other gaseous mediators. Cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase are the principal enzymes involved in H2S production. We have recently studied H2S metabolism in the plasma of chronic hemodialysis patients and reported that its levels are significantly decreased. The plausible mechanism lies in the transcription inhibition of the cystathionine γ-lyase gene. The finding could be of importance considering that hypertension and high cardiovascular mortality are characteristic in these patients.

1.
Gadalla MM, Snyder SH: Hydrogen sulfide as a gasotransmitter. J Neurochem DOI: 10.1111/j.1471-4159.2010.06580.x.
2.
Kimura H: Hydrogen sulfide: its production, release and functions. Amino Acids DOI: 10.1007/s00726-010-0510-x.
3.
Lefer DJ: A new gaseous signaling molecule emerges: cardioprotective role of hydrogen sulfide. Proc Natl Acad Sci USA 2007;104:17907–17908.
4.
Szabo C: Hydrogen sulphide and its therapeutic potential. Nat Rev 2007;6:917–935.
5.
Li L, Moore PK: Putative biological roles of hydrogen sulfide in health and disease: a breath of not so fresh air? Trends Pharmacol Sci 2008;29:84–90.
6.
Tripatara P, Patel NSA, Collino M, Gallicchio M, Kieswich J, Castiglia S, Benedetti E, Stewart KN, Brown PAJ, Yaqoob MM, Fantozzi R, Thiemermann C: Generation of endogenous hydrogen sulfide by cystathionine γ-lyase limits renal ischemia/reperfusion injury and dysfunction. Lab Invest 2008;88:1038–1048.
7.
Xia M, Chen L, Muh RW, Li PL, Li N: Production and actions of hydrogen sulfide, a novel gaseous bioactive substance, in the kidneys. J Pharmacol Exp Ther 2009;329:1056–1062.
8.
Wu N, Siow YL, Karmin O: Ischemia/reperfusion reduces transcription factor SP1 mediated cystathionine beta-synthase expression in the kidney. J Biol Chem DOI: 10.1074/jbc.M110.132142.
9.
Beltowski J: Hypoxia in the renal medulla: implications for hydrogen sulfide signaling. J Pharmacol Exp Ther DOI: 10.1124/jpet.110.166637.
10.
Chen X, Jhee K, Kruger WD: Production of the neuromodulator H2S by cystathionine β-synthase via the condensation of cysteine and homocysteine. J Biol Chem 2004;279:52082–52086.
11.
Shibuya N, Mikami Y, Kimura Y, Nagahara N, Kimura H: Vascular endothelium expresses 3-mercaptopyruvate sulfurtransferase and produces hydrogen sulfide. J Biochem 2009;146:623–626.
12.
Benavides GA, Squadrito GL, Mills RW, Patel HD, Isbell TS, Patel RP, Darley-Usmar VM, Doeller JE, Kraus DW: Hydrogen sulfide mediates the vasoactivity of garlic. Proc Natl Acad Sci USA 2007;104:17977–17982.
13.
Budoff MJ, Ahmadi N, Gul KM, Liu ST, Flores FR, Tiano J, Takasu J, Miller E, Tsimikas S: Aged garlic extract supplemented with B vitamins, folic acid andL-arginine retards the progression of subclinical atherosclerosis: a randomized clinical trial. Prev Med 2009;49:101–107.
14.
Yang G, Wu L, Jiang B, Yang W, Qi J, Cao K, Meng Q, Mustafa AK, Mu W, Zhang S, Snyder SH, and Wang R: H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase. Science 2008;322:587–590.
15.
Perna AF, Luciano MG, Ingrosso D, Raiola I, Pulzella P, Sepe I, Lanza D, Violetti E, Capasso R, Lombardi C, De Santo NG: Hydrogen sulfide, the third gaseous signaling molecule with cardiovascular properties, is decreased in hemodialysis patients. J Ren Nutr 2010;20(suppl):S11–S14.
16.
Lu M, Liu Y, Goh HS, Wang JJ, Yong QC, Wang R, Bian JS: Hydrogen sulfide inhibits plasma renin activity. J Am Soc Nephrol 2010;21:993–1002.
17.
Wang Y, Zhao X, Jin H, Wei H, Li W, Bu D, Tang X, Ren Y, Tang X, Du J: Role of hydrogen sulfide in the development of atherosclerotic lesions in apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol 2008;29:173–179.
18.
D’Emanuele di Villa Bianca R, Sorrentino R, Maffia P, Mirone V, Imbimbo C, Fusco F, De Palma R, Ignarro LJ, Cirino G: Hydrogen sulfide as a mediator of human corpus cavernosum smooth-muscle relaxation. Proc Natl Acad Sci USA 2009;106:4513–4518.
19.
Wu L, Yang W, Jia X, Yang G, Duridanova D, Cao K, Wang R: Pancreatic islet overproduction of H2S and suppressed insulin release in Zucker diabetic rats. Lab Invest 2009;89:59–67.
20.
Ali MY, Whiteman M, Low CM, Moore PK: Hydrogen sulphide reduces insulin secretion from HIT-T15 cells by a KATP channel-dependent pathway. J Endocrinol 2007;195:1205–1212.
21.
Yang G, Yang W, Wu L, Wang R: H2S, endoplasmic reticulum stress, and apoptosis of insulin-secreting beta cells. J Biol Chem 2007;292:16567–16576.
22.
Brancaleone V, Roviezzo F, Velleco V, De Gruttola L, Bucci M, Cirino G: Biosynthesis of H2S is impaired in non-obese diabetic (NOD) mice. Br J Pharmacol 2008;155:673–680.
23.
Whiteman M, Gooding KM, Whatmore JL, Ball CI, Mawson D, Skinner K, Tooke JE, Shore AC: Adiposity is a major determinant of plasma levels of the novel vasodilator hydrogen sulfide. Diabetologia 2010;53:1722–1726.
24.
Sen U, Basu P, Abe OA, Givvimani S, Tyagi N, Metreveli N, Shah KS, Passmore JC, Tyagi SC: Hydrogen sulfide ameliorates hyperhomocysteinemia-associated chronic renal failure. Am J Physiol Ren Physiol 2009;297:F410–F419.
25.
Jain SK, Bull R, Rains JL, Bass PF, Levine SN, Reddy S, McVie R, Bocchini JA: Low levels of hydrogen sulfide in the blood of diabetes patients and streptozotocin-treated rats causes vascular inflammation? Antioxid Redox Signal 2010;12:1333–1337.
26.
Kaneko Y, Kimura Y, Kimura H, Niki I: L-cysteine inhibits insulin release from the pancreatic beta-cell: possible involvement of metabolic production of hydrogen sulfide, a novel gasotransmitter. Diabetes 2006;55:1391–1397.
27.
Mustafa AK, Gadalla MM, Sen N, Kim S, Mu W, Gazi SK, Barrow RK, Yang G, Wang R, Snyder SH: H2S signals through protein S-sulfhydration. Sci Signal 2009;2:ra72.
28.
Perna AF, Ingrosso D, Violetti E, Luciano MG, Sepe I, Lanza D, Capasso R, Ascione E, Raiola I, Lombardi C, Stenvinkel P, Massy Z, De Santo NG: Hyperhomocysteinemia in uremia – a red flag in a disrupted circuit. Semin Dial 2009;22:351–356.
29.
Perna AF, Luciano MG, Ingrosso D, Pulzella P, Sepe I, Lanza D, Violetti E, Capasso R, Lombardi C, De Santo NG: Hydrogen sulphide-generating pathways in haemodialysis patients: a study on relevant metabolites and transcriptional regulation of genes encoding for key enzymes. Nephrol Dial Transplant 2009;24:3756–3763.
30.
Elsey DJ, Fowkes RC, Baxter GF: Regulation of cardiovascular cell function by hydrogen sulfide (H2S). Cell Biochem Funct DOI: 10.1002/cbf.1618.
31.
Bos EM, Leuvenink HGD, Snijder PM, Kloosterhuis NJ, Hillebrands J, Leemans JC, Florquin S, van Goor H: Hydrogen sulfide-induced hypometabolism prevents renal ischemia/reperfusion injury. J Am Soc Nephrol 2009;20:1901–1905.
32.
Chiku T, Dominique Padovani D, Zhu W, Singh S, Vitvitsky V, Banerjee R: H2S biogenesis by human cystathionine γ-lyase leads to the novel sulfur metabolites lanthionine and homolanthionine and is responsive to the grade of hyperhomocysteinemia. J Biol Chem 2009;284:11601–11612.
33.
Mancardi D, Penna C, Merlino A, Del Soldato P, Wink DA, Pagliaro P: Physiological and pharmacological features of the novel gasotransmitter: hydrogen sulfide. Biochim Biophys Acta 2009;1787:864–872.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.