Role of hydrogen sulphide in regulatory functions

24 March 2011
Written by Varaksin A.A., Puschina E.V.

  UDK: 546.221.1:612.822:616 | Pages: 27-34 | Read full textDownload PDF 


The paper provides new published data and results of authors’ studies on physiology and pathology of hydrogen sulphide gas transmitter. The hydrogen sulphide is synthesised from cysteine by pyridoxal‑5’‑phosphate‑dependent enzymes of cystathionine‑β‑synthase or cystathionine‑γ‑lyase. It stimulates the ATP‑dependent potassium channels in the vascular smooth muscle cells, neurons, cardiomyocytes, and β‑cells of pancreatic gland, thus being involved in regulation of vasomotor tone, reduction of cardiomyocytes, neurotransmission, and insulin secretion. The authors describe effects of hydrogen sulphide‑inducing systems on the pathogenesis of arterial and lung hypertension, Alzheimer disease, and liver cirrhosis.

Links to authors:

A.A. Varaksin, E.V. Puschina
A.V. Zhirmunsky Institute of Marine Biology (17 Palchevskogo St. Vladivostok 690041 Russian Federation)

  1. Abe K., Kimura H. The possible role of hydrogen sulfide as an endogenous neuromodulator, J. Neurosci. 1996. Vol. 16. P. 1066–1071.
  2. Abel T., Nguyen P.V., Barad M. et al. Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus‑based long‑term memory, Cell. 1997. Vol. 88. P. 615–626. 
  3. Ali M.Y., Ping C.Y., Mok Y.Y. et al. Regulation of vascular nitric oxide in vitro and in vivo; a new role for endogenous hydrogen sulphide? Br. J. Pharmacol. 2006. Vol. 149. P. 625–634.
  4. Ali M.Y., Whiteman M., Low C.M., Moore P.K. Hydrogen sulphide reduces insulin secretion from HIT‑T15 cells by a KATP channel‑dependent pathway, J. Endocrinol. 2007. Vol. 195. P. 105–112.
  5. Attene‑Ramos M.S., Wagner E.D., Plewa M.J., Gaskins H.R. Evidence that hydrogen sulfide is a genotoxic agent, Mol. Cancer Res. 2006. Vol. 4. P. 9–14.
  6. Bhatia M., Sidhapuriwala J., Moochhala S.M., Moore P.K. Hydrogen sulphide is a mediator of carrageenan‑induced hindpaw oedema in the rat, Br. J. Pharmacol. 2005. Vol. 145. P. 141–144.
  7. Bhatia M., Zhi L., Zhang H., Ng S.W., Moore P.K. Role of substance P in hydrogen sulfide‑induced pulmonary inflammation in mice, Am. J. Physiol. Lung Cell Mol. Physiol. 2006. Vol. 291. P. 896–904.
  8. Bicker G. STOP and GO with NO: nitric oxide as a regulator of cell motility in simple brains, BioEssays. 2005. Vol. 27. P. 495–505.
  9. Braet K., Cabooter L., Paemeleire K., Leybaert L. Calcium signal communication in the central nervous system, Biol. Cell. 2004. Vol. 96. P. 79–91.
  10. Bucci M., Mirone V., Di Lorenzo A. et al. Hydrogen sulphide is involved in testosterone vascular effect, Eur. Urol. 2009. Vol. 56. P. 378–383.
  11. Chen X., Jhee K.H., Kruger W.D. Production of the neuromodulator H2S by cystathionine beta‑synthase via the condensation of cysteine and homocysteine, J. Biol. Chem. 2004. Vol. 279. P. 52082–52086.
  12. Cheng Y., Ndisang J.F., Tang G., Cao K., Wang R. Hydrogen sulfide‑induced relaxation of resistance mesenteric artery beds of rats, Am. J. Physiol. Heart Circ. Physiol. 2004. Vol. 287. P. H2316–H2323.
  13. Dawe G.S., Han S.P., Bian J.S., Moore P.K. Hydrogen sulphide in the hypothalamus causes an ATP‑sensitive K+‑channel‑dependent decrease in blood pressure in freely moving rats, Neuroscience. 2008. Vol. 152. P. 169–177.
  14. Deplancke B., Gaskins H.R. Hydrogen sulfide induces serumindependent cell cycle entry in nontransformed rat intestinal epithelial cells, FASEB J. 2003. Vol. 17. P. 1310–1312.
  15. Distrutti E., Sediari L., Mencarelli A. et al. Evidence that hydrogen sulfide exerts antinociceptive effects in the gastrointestinal tract by activating KATP channels, J. Pharmacol. Exp. Ther. 2006. Vol. 316. P. 325–335.
  16. Distrutti E., Mencarelli A., Santucci L. et al. The methionine connection: homocysteine and hydrogen sulfide exert opposite effects on hepatic microcirculation in rats, Hepatology. 2008. Vol. 47. P. 659–667.
  17. Dombkowski R.A., Russell M.J., Olson K.R. Hydrogen sulfide as an endogenous regulator of vascular smooth muscle tone in trout, Am. J. Physiol. Regul. Integr. Comp. Physiol. 2004. Vol. 286. P. R678–R685.
  18. Dombkowski R.A., Russell M.J., Schulman A.A. et al. Vertebrate phylogeny of hydrogen sulfide vasoactivity, Am. J. Physiol. Regul. Integ.r Comp. Physiol. 2005. Vol. 288. P. R243–R252.
  19. Du J., Hui Y., Cheung Y., Bin G. et al. The possible role of hydrogen sulfide as a smooth muscle cell proliferation inhibitor in rat cultured cells, Heart Vessels. 2004. Vol. 19. P. 75–80.
  20. Eto K., Asada T., Arima K. et al. Brain hydrogen sulfide is severely decreased in Alzheimer’s disease, Biochem. Biophys. Res. Commun. 2002. Vol. 293. P. 1485–1488.
  21. Eto K., Awata S., Nakayama K. et al. Changes in cystathionine gamma‑lyase in various regions of rat brain during development, Biochem. Mol. Biol. Int. 1995. Vol. 35. P. 1331–1338.
  22. Farber K., Kettenmann H. Physiology of microglial cells, Brain Res. Brain Res. Rev. 2005. Vol. 48. P. 133–143.
  23. Fiorucci S., Antonelli E., Distrutti E. et al. Inhibition of hydrogen sulfide generation contributes to gastric injury caused by non‑steroidal anti‑inflammatory drugs, astroenterology. 2005. Vol. 129. P. 1210–1224.
  24. Fiorucci S., Antonelli E., Mencarelli A. et al. The third gas: H2S regulates perfusion pressure in both the isolated and perfused normal rat liver and in cirrhosis, Hepatology. 2005. Vol. 42. P. 539–548.
  25. Fiorucci S., Distrutti E., Cirino G., Wallace J.L. The emerging roles of hydrogen sulfide in the gastrointestinal tract and liver, Gastroenterology. 2006. Vol. 131. P. 259–271.
  26. Fujii K., Sakuragawa T., Kashiba M. et al. Hydrogen sulfide as an endogenous modulator of biliary bicarbonate excretion in the rat liver, Antioxid. Redox Signal. 2005. Vol. 7. P. 788–794.
  27. Furchgott R.F., Zawadzki J.V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine, Nature. 1980. Vol. 288. P. 373–376.
  28. Furne J., Springfield J., Koenig T. et al. Oxidation of hydrogen sulfide and methanethiol to thiosulfate by rat tissues: a specialized function of the colonic mucosa, Bioshem. Pharmacol. 2001. Vol. 6. P. 255–259.
  29. García‑Bereguiaín M.A., Samhan‑Arias A.K., Martín‑Romero F.J., Gutiérrez‑Merino C. Hydrogen sulfide raises cytosolic calcium in neurons through activation of L‑type Ca2+channels, Antioxid. Redox Signal. 2008. Vol. 10. P. 31–42.
  30. García‑Tevijano E.R., Berasain C., Rodríguez J.A. et al. Hyperhomocysteinemia in liver cirrhosis: mechanisms and role in vascular and hepatic fibrosis, Hypertension. 2001. Vol. 38. P. 1217–1221.
  31. Gardiner S.M., Kemp P.A., March J.E., Bennett T. Regional haemodynamic responses to infusion of lipopolysaccharide in conscious rats: effects of pre‑ or post‑treatment with glibenclamide, Br. J. Pharmacol. 1999. Vol. 128. P. 1772–1778.
  32. Geng B., Yang J., Qi Y. et al. H2S generated by heart in rat and its effects on cardiac function, Biochem. Biophys. Res. Commun. 2004. Vol. 313. P. 362–368.
  33. Guzmán M.A., Navarro M.A., Carnicer R. et al. Cystathionine β‑synthase is essential for female reproductive function, Human Molecular Genetics. 2006. Vol. 15. P. 3168–3176.
  34. Han Y., Qin J., Chang X., Yang Z. et al. Modulating effect of hydrogen sulfide on gamma‑aminobutyric acid B receptor in recurrent febrile seizures in rats, Neurosci. Res. 2005. Vol. 53. P. 216–219.
  35. Hosoki R., Matsuki N., Kimura H. The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide, Biochem. Biophys. Res. Commun. 1997. Vol. 237. P. 527–531.
  36. Hui Y., Du J., Tang C., Bin G., Jiang H. Changes in arterial hydrogen sulfide (H2S) content during septic shock and endotoxic shock in rats, J. Infect. 2003. Vol. 47 P. 155–160.
  37. Huycke M.M., Gaskins H.R. Commensal bacteria, redox stress, and colorectal cancer: mechanisms and models, Exp. Biol. Med. 2004. Vol. 229. P. 586–597.
  38. Jacobs R.L., House J.D., Brosnan M.E., Brosnan J.T. Effects of streptozotocin‑induced diabetes and of insulin treatment on homocysteine metabolism in the rat, Diabetes. 1998. Vol. 47. P. 1967–1970.
  39. Kage S., Kashimura S., Ikeda H., Kudo K., Ikeda N., Fatal and nonfatal poisoning by hydrogen sulfide at an industrial waste site, J. Forensic Sci. 2002. Vol. 47. P. 652–655.
  40. Kamoun P., Belardinelli M.C., Chabli A. et al. Endogenous hydrogen sulfide overproduction in Down syndrome, Am. J. Med. Genet. 2003. Vol. 116. P. 310–311.
  41. Kamoun P. Mental retardation in Down syndrome: a hydrogen sulfide hypothesis, Med. Hypotheses. 2001. Vol. 57. P. 389–392.
  42. Kim Y.S., Joh T.H. Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson’s disease, Exp. Mol. Med. 2006. Vol. 38. P. 333–347.
  43. Kimura H. Hydrogen sulfide induces cyclic AMP and modulates the NMDA receptor, Biochem. Biophys. Res. Commun. 2000. Vol. 267. P. 129–133.
  44. Kimura Y., Dargusch R., Schubert D., Kimura H. Hydrogen sulfide protects HT22 neuronal cells from oxidative stress, Antioxid. Redox. Signal. 2006. Vol. 8. P. 661–670.
  45. Kimura Y., Kimura H. Hydrogen sulfide protects neurons from oxidative stress, FASEB J. 2004. Vol. 18. 1165–1167.
  46. Koehler R.C., Gebremedhin D., Harder D.R. Role of astrocytes in cerebrovascular regulation, J. Appl. Physiol. 2006. Vol. 100. P. 307–317.
  47. Lee S.W., Hu Y.S., Hu L.F. et al. Hydrogen sulphide regulates calcium homeostasis in microglial cells, Glia. 2006. Vol. 54. P. 116–124.
  48. Leschelle X., Goubern M., Andriamihaja M. et al. Adaptative metabolic response of human colonic epithelial cells to the adverse effects of the luminal compound sulfide, Biochim. Biophys. Acta. 2005. Vol. 1725, P. 201–212.
  49. Li L., Bhatia M., Zhu Y.Z. et al. Hydrogen sulfide is a novel mediator of lipopolysaccharide‑induced inflammation in the mouse, FASEB J. 2005. Vol. 19. P. 1196–1198.
  50. Li X.H., Du J.B., Bu D.F. et al. Sodium hydrosulfide alleviated pulmonary vascular structural remodeling induced by high pulmonary blood flow in rats, Acta Pharmacol. Sin. 2006. Vol. 27. P. 971–980.
  51. Liang R., Yu W.D., Du J.B. et al. Cystathionine beta synthase participates in murine oocyte maturatione mediated by homocysteine, Reprod. Toxicol. 2007. Vol. 24. P. 89–96.
  52. Liang R., Yu W.D., Du J.B. et al. Localization of cystathionine beta synthase in mice ovaries and its expression profile during follicular development, Chin. Med. J. 2006. Vol. 119. P. 1877–1883.
  53. Luberda Z. The role of glutathione in mammalian gametes, Reprod. Biol. 2005. Vol. 5. P. 5–17.
  54. Mariggio M.A., Pettini F., Fumarulo R. Sulfide influence on polymorphonuclear functions: a possible role for Ca2+involvement, Immunopharmacol. Immunotoxicol. 1997. Vol. 19. P. 393–404.
  55. Mok Y.Y., Atan M.S., Yoke P.C. et al. Role of hydrogen sulphide in haemorrhagic shock in the rat: protective effect of inhibitors of hydrogen sulphide biosynthesis, Br. J. Pharmacol. 2004. Vol. 143. P. 881–889.
  56. Moore P.K., Bhatia M., Moochhala S. Hydrogen sulfide: from the smell of the past to the mediator of the future? Trends Pharmacol. Sci. 2003. Vol. 24. P. 609–611.
  57. Morale M.C., Serra P.A., L’Episcopo F. et al. Estrogen, neuroin‑flammation and neuroprotection in Parkinson’s disease: glia dictates resistance versus vulnerability to neurodegeneration, Neuroscience. 2006. Vol. 138. P. 869–878.
  58. Murphy M.E., Brayden J.E. Nitric oxide hyperpolarizes rabbit mesenteric arteries via ATP‑sensitive potassium channels, J. Physiol. 1995. Vol. 486. P. 47–58.
  59. Oh G.S., Pae H.O., Lee B.S. et al. Hydrogen sulfide inhibits nitric oxide production and nuclear factor‑kappa B via heme oxygenase‑1 expression in RAW264.7 macrophages stimulated with lipopolysaccharide, Free Radic. Biol. Med. 2006. Vol. 41. P. 106–119.
  60. Olson K.R., Donald J.A. Nervous control of circulation The role of gasotransmitters, NO, CO, and H2S, Acta histochem. 2009. Vol. 111. P. 244–256.
  61. Picton R., Eggo M.C., Merrill G.A. et al. Mucosal protection against sulphide: importance of the enzyme rhodanese, Gut. 2002. Vol. 50. P. 201–205.
  62. Platel J.C., Stamboulian S., Nguyen I., Bordey A. Neurotransmitter signaling in postnatal neurogenesis: the first leg, Brain Res. Rev. 2010. Vol. 63. P. 60–71.
  63. Pushchina Е.V., Varaksin A.A., Obukhov D.K. Cystathionine β‑synthase in the CNS of masu salmon Oncorhynchus masou (Salmonidae) and carp Cyprinus carpio (Cyprinidae), Neurochem. J. 2011. Vol. 5. No. 1. P. 24–34.
  64. Pushchina E.V., Karpenko A.A. The relationships between neurons containing dopamine and nitric oxide synthase in the encephalon of cyprinid teleost, Proc. 11th Multidiscip. Intern. Neurosci. and Biol. Psychiatry Conf. “Stress and Behavior”. St‑Petersburg, 2008. P. 62.
  65. Pushchina Е.V., Fleishman M. Yu., Timoshin S.S. Proliferative zones in the brain of the Amur sturgeon fry. Interaction with neuromeres and migration of secondary matrix zones, Rus. J. Devel. Biol. 2007. Vol. 38. No. 5. P. 286–293.
  66. Rinaldi L., Gobbi G., Pambianco M. et al. Hydrogen sulfide prevents apoptosis of human PMN via inhibition of p38 and caspase 3, Lab. Invest. 2006. Vol. 86. P. 391–397.
  67. Schicho R., Krueger D., Zeller F. et al. Hydrogen sulfide is a novel prosecretory neuromodulator in the Guinea‑pig and human colon, Gastroenterology. 2006. Vol. 131. P. 1542–1552.
  68. Searsy D.G. HS‑:O2 oxidoreductase activity of Cu, Zn superoxide dismutase, Arch. Biochem. Biophis. 1996. Vol. 334. P. 50–58.
  69. Srilatha B., Adaikan P.G., Li L., Moore P.K. Hydrogen sulphide: a novel endogenous gasotransmitter facilitates erectile function, J. Sex Med. 2007. Vol. 4. P. 1304–1311.
  70. Srilatha B., Adaikan P.G., Moore P.K. Possible role for the novel gasotransmitter hydrogen sulphide in erectile dysfunction ‑ a pilot study, Eur. J. Pharmacol. 2006. Vol. 535. P. 280–282.
  71. Stipanuk M.H. Sulfur amino acid metabolism: pathways for production and removal of homocysteine and cysteine, Ann. Rev. Nutr. 2004. Vol. 24. P. 539–577.
  72. Teague B., Asiedu S., Moore P.K. The smooth muscle relaxant effect of hydrogen sulphide in vitro: evidence for a physiological role to control intestinal contractility, Br. J. Pharmacol. 2002. Vol. 137. P. 139–145.
  73. Trevisani M., Patacchini R., Nicoletti P. et al. Hydrogen sulfide causes vanilloid receptor 1‑mediated neurogenic inflammation in the airways, Br. J. Pharmacol. 2005. Vol. 145. P. 1123–1131.
  74. Ugrumov M.V. Non‑dopaminergic neurons partly expressing dopaminergic phenotype: distribution in the brain, development and functional significance, J. Chem. Neuroanat. 2009. Vol. 38. P. 241–256.
  75. Ugrumov M.V. Developing brain as an endocrine organ: a paradoxical reality, Neurochem. Res. 2010. Vol. 35. P. 837–850.
  76. Wang R. Two’s company, three’s a crowd: can H2S be the third endogenous gaseous transmitter? FASEB J. 2002. Vol. 16. P. 1792–1798.
  77. Wojtera M., Sikorska B., Sobow T., Liberski P.P. Microglial cells in neurodegenerative disorders, Folia Neuropathol. 2005. Vol. 43. P. 311–321.
  78. Wong P.T., Qu K., Chimon G.N. et al. High plasma cysteine level may indicate poor clinical outcome in patients with acute stroke: possible involvement of hydrogen sulfide, J. Neuropathol. Exp. Neurol. 2006. Vol. 65. P. 109–115.
  79. Wu S.Y., Pan C.S., Geng B. et al. Hydrogen sulfide ameliorates vascular calcification induced by vitamin D3 plus nicotine in rats, Acta Pharmacol. Sin. 2006. Vol. 27. P. 299–306.
  80. Wu G., Fang Y.Z., Yang S. et al. Glutathione metabolism and its implications for health, J. Nutr. 2004. Vol. 134. P. 489–492.
  81. Yan H., Du J., Tang C. The possible role of hydrogen sulfide on the pathogenesis of spontaneous hypertension in rats, Biochem. Biophys. Res. Commun. 2004. Vol. 313. P. 22–27.
  82. Yang G., Sun X., Wang R. Hydrogen sulfide‑induced apoptosis of human aorta smooth muscle cells via the activation of mitogenactivated protein kinases and caspase‑3, FASEB J. 2004. Vol. 18. P. 1782–1784.
  83. Yang G., Wu L., Wang R. Pro‑apoptotic effect of endogenous H2S on human aorta smooth muscle cells, FASEB J. 2006. Vol. 20. P. 553–555.
  84. Yang W., Yang G., Jia X. et al. Activation of KATP channels by H2S in rat insulin‑secreting cells and the underlying mechanisms, J. Physiol. 2005. Vol. 569. P. 519–531.
  85. Yet S.F., Pellacani A., Patterson C. et al. Induction of heme oxygenase‑1 expression in vascular smooth muscle cells. A link to endotoxic shock, J. Biol. Chem. 1997. Vol. 272. P. 4295–4301.
  86. Yusuf M., Kwong Huat B.T., Hsu A. et al. Streptozotocin‑induced diabetes in the rat is associated with enhanced tissue hydrogen sulfide biosynthesis, Biochem. Biophys. Res. Commun. 2005. Vol. 333. P. 1146–1152.
  87. Zanardo R.C., Brancaleone V., Distrutti E. et al. Hydrogen sulfide is an endogenous modulator of leukocyte‑mediated inflammation, FASEB J. 2006. Vol. 20. P. 2118–2120.
  88. Zhang H., Zhi L., Moore P.K., Bhatia M. Role of hydrogen sulfide in cecal ligation and puncture‑induced sepsis in the mouse, Am. J. Physiol. Lung. Cell. Mol. Physiol. 2006. Vol. 290. P. L1193–L1201.
  89. Zhao W., Zhang J., Lu Y., Wang R. The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener, EMBO J. 2001. Vol. 20. P. 6008–6016.
  90. Zhong G., Chen F., Cheng Y. et al. The role of hydrogen sulfide generation in the pathogenesis of hypertension in rats induced by inhibition of nitric oxide synthase, J. Hypertens. 2003. Vol. 21. P. 1879–1885.
  91. Zhu Y.Z., Wang Z.J., Ho P. et al. Hydrogen sulfide and its possible roles in myocardial ischemia in experimental rats, J. Appl. Physiol. 2007. Vol. 102. P. 261–268.


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