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Endogenous Production of Hydrogen Sulfide in Isolated Bovine Eye

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Abstract

Hydrogen sulfide (H2S) is a novel gasotransmitter with physiological and pathological functions in vascular homeostasis, cardiovascular system and central nervous system. In the present study, we determined the endogenous levels of H2S in various tissues of the bovine eye. We also examined the basal levels of H2S in response to donors (sodium hydrosulfide, NaHS and sodium sulfide, Na2S), substrate (l-cysteine), inhibitors (propargylglycine, PAG and aminooxyacetic acid, AOA) and activator (S-adenosyl-l-methionine, SAM) of this gas in the bovine retina. H2S was measured using a well established spectrophotometric method. The highest concentration of endogenous H2S was detected in cornea (19 ± 2.85 nmoles/mg protein, n = 6) and retina (17 ± 2.1 nmoles/mg protein, n = 6). Interestingly, H2S was not present in vitreous humor. The inhibitors of CSE and CBS; PAG (1 mM) and AOA (1 mM), significantly attenuated the production of H2S in the bovine retina by 56.8 and 42%, respectively. On the other hand the activator of CBS; SAM (100 μM), H2S donors; NaHS (1 μM) and Na2S (100 μM), significantly increased endogenous levels of H2S in bovine retina. l-cysteine (10–300 μM) produced a significant (P < 0.05) concentration-dependent increase in H2S levels reaching a maximal at 300 μM. We conclude that H2S is endogenously produced in various tissues of the isolated bovine eye. Moreover, endogenous levels of H2S are enhanced in the presence of substrate (l-cysteine), an activator of CBS (SAM) and H2S donors but are blocked by inhibitors of enzymes that synthesize this gas in neural retina.

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Abbreviations

H2S:

Hydrogen sulfide

CSE:

Cystathionine γ-lyase

CBS:

Cystathionine β-synthase

PAG:

Propargylglycine

AOA:

Aminooxyacetic acid

SAM:

S-adenosyl-l-methionine

NaHS:

Sodium hydrosulfide

Na2S:

Sodium sulfide

References

  1. Qu K, Lee SW, Bian JS et al (2008) Hydrogen sulfide: neurochemistry and neurobiology. Neurochem Int 52:155–165

    Article  PubMed  CAS  Google Scholar 

  2. Lowicka E, Beltowski J (2007) Hydrogen sulfide (H2S) - the third gas of interest for pharmacologists. Pharmacol Rep 59:4–24

    PubMed  CAS  Google Scholar 

  3. Tan BH, Wong PT, Bian JS (2010) Hydrogen sulfide: a novel signaling molecule in the central nervous system. Neurochem Int 56:3–10

    Article  PubMed  CAS  Google Scholar 

  4. Tay AS, Hu LF, Lu M et al (2010) Hydrogen sulfide protects neurons against hypoxic injury via stimulation of ATP-sensitive potassium channel/protein kinase C/extracellular signal-regulated kinase/heat shock protein 90 pathway. Neuroscience 167:277–286

    Article  PubMed  CAS  Google Scholar 

  5. Li L, Moore PK (2007) An overview of the biological significance of endogenous gases: new roles for old molecules. Biochem Soc Trans 35:1138–1141

    Article  PubMed  CAS  Google Scholar 

  6. Erickson PF, Maxwell IH, Su LJ et al (1990) Sequence of cDNA for rat cystathionine gamma-lyase and comparison of deduced amino acid sequence with related Escherichia coli enzymes. Biochem J 269:335–340

    PubMed  CAS  Google Scholar 

  7. Stipanuk MH, Beck PW (1982) Characterization of the enzymic capacity for cysteine desulphhydration in liver and kidney of the rat. Biochem J 206:267–277

    PubMed  CAS  Google Scholar 

  8. Swaroop M, Bradley K, Ohura T et al (1992) Rat cystathionine beta-synthase. Gene organization and alternative splicing. J Biol Chem 267:11455–11461

    PubMed  CAS  Google Scholar 

  9. Hosoki R, Matsuki N, Kimura H (1997) The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide. Biochem Biophys Res Commun 237:527–531

    Article  PubMed  CAS  Google Scholar 

  10. Levonen AL, Lapatto R, Saksela M et al (2000) Human cystathionine gamma-lyase: developmental and in vitro expression of two isoforms. Biochem J 347(Pt 1):291–295

    Article  PubMed  CAS  Google Scholar 

  11. Lu Y, O’Dowd BF, Orrego H et al (1992) Cloning and nucleotide sequence of human liver cDNA encoding for cystathionine gamma-lyase. Biochem Biophys Res Commun 189:749–758

    Article  PubMed  CAS  Google Scholar 

  12. Meier M, Janosik M, Kery V et al (2001) Structure of human cystathionine beta-synthase: a unique pyridoxal 5’-phosphate-dependent heme protein. EMBO J 20:3910–3916

    Article  PubMed  CAS  Google Scholar 

  13. van der Molen EF, Hiipakka MJ, van Lith-Zanders H et al (1997) Homocysteine metabolism in endothelial cells of a patient homozygous for cystathionine beta-synthase (CS) deficiency. Thromb Haemost 78:827–833

    PubMed  Google Scholar 

  14. Yap S, Naughten ER, Wilcken B et al (2000) Vascular complications of severe hyperhomocysteinemia in patients with homocystinuria due to cystathionine beta-synthase deficiency: effects of homocysteine-lowering therapy. Semin Thromb Hemost 26:335–340

    Article  PubMed  CAS  Google Scholar 

  15. Abe K, Kimura H (1996) The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci 16:1066–1071

    PubMed  CAS  Google Scholar 

  16. Richardson CJ, Magee EA, Cummings JH (2000) A new method for the determination of sulphide in gastrointestinal contents and whole blood by microdistillation and ion chromatography. Clin Chim Acta 293:115–125

    Article  PubMed  CAS  Google Scholar 

  17. Gadalla MM, Snyder SH (2010) Hydrogen sulfide as a gasotransmitter. J Neurochem 113:14–26

    Article  PubMed  CAS  Google Scholar 

  18. Persa C, Osmotherly K, Chao-Wei Chen K et al (2006) The distribution of cystathionine beta-synthase (CBS) in the eye: implication of the presence of a trans-sulfuration pathway for oxidative stress defense. Exp Eye Res 83:817–823

    Article  PubMed  CAS  Google Scholar 

  19. Pong WW, Stouracova R, Frank N et al (2007) Comparative localization of cystathionine beta-synthase and cystathionine gamma-lyase in retina: differences between amphibians and mammals. J Comp Neurol 505:158–165

    Article  PubMed  CAS  Google Scholar 

  20. De Luca G, Ruggeri P, Macaione S (1974) Cystathionase activity in rat tissues during development. Ital J Biochem 23(6):371–379

    PubMed  Google Scholar 

  21. Kraus JP, Kozich V (2001) Cystathionine B synthase and its deficiency. In: Carmel R, Jacobsen DW (eds) Homocysteine in health and disease. Cambridge University Press, Cambridge, pp 223–243

    Google Scholar 

  22. Mudd SH, Levy HL, Kraus JP (2001) Disorders of trans-sulfuration. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Kinzler K, Vogelstein B (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 2007–2056

    Google Scholar 

  23. Kulkarni KH, Monjok EM, Zeyssig R et al (2009) Effect of hydrogen sulfide on sympathetic neurotransmission and catecholamine levels in isolated porcine iris-ciliary body. Neurochem Res 34:400–406

    Article  PubMed  CAS  Google Scholar 

  24. Monjok EM, Kulkarni KH, Kouamou G et al (2008) Inhibitory action of hydrogen sulfide on muscarinic receptor-induced contraction of isolated porcine irides. Exp Eye Res 87:612–616

    Article  PubMed  CAS  Google Scholar 

  25. Opere CA, Monjok EM, Kulkarni KH et al (2009) Regulation of [3H] D-aspartate release from mammalian isolated retinae by hydrogen sulfide. Neurochem Res 34:1962–1968

    Article  PubMed  CAS  Google Scholar 

  26. Ohia SE, Opere CA, Monjok EM et al (2010) Role of hydrogen sulfide production in inhibitory action of l-cysteine on isolated porcine irides. Curr Eye Res 35:402–407

    Article  PubMed  CAS  Google Scholar 

  27. Njie-Mbye YF, Bongmba OY, Onyema CC et al (2010) Effect of hydrogen sulfide on cyclic AMP production in isolated bovine and porcine neural retinae. Neurochem Res 35:487–494

    Article  PubMed  CAS  Google Scholar 

  28. Xia M, Chen L, Muh RW et al (2009) Production and actions of hydrogen sulfide, a novel gaseous bioactive substance, in the kidneys. J Pharmacol Exp Ther 329:1056–1062

    Article  PubMed  CAS  Google Scholar 

  29. Kimura H (2010) Hydrogen sulfide: from brain to gut. Antioxid Redox Signal 12:1111–1123

    Article  PubMed  CAS  Google Scholar 

  30. Eto K, Ogasawara M, Umemura K et al (2002) Hydrogen sulfide is produced in response to neuronal excitation. J Neurosci 22:3386–3391

    PubMed  CAS  Google Scholar 

  31. Eto K, Kimura H (2002) A novel enhancing mechanism for hydrogen sulfide-producing activity of cystathionine beta-synthase. J Biol Chem 277:42680–42685

    Article  PubMed  CAS  Google Scholar 

  32. Eto K, Asada T, Arima K et al (2002) Brain hydrogen sulfide is severely decreased in Alzheimer’s disease. Biochem Biophys Res Commun 293:1485–1488

    Article  PubMed  CAS  Google Scholar 

  33. Finkelstein JD, Kyle WE, Martin JL et al (1975) Activation of cystathionine synthase by adenosylmethionine and adenosylethionine. Biochem Biophys Res Commun 66:81–87

    Article  PubMed  CAS  Google Scholar 

  34. Jensen KK, Geoghagen NS, Jin L et al (2011) Pharmacological activation and genetic manipulation of cystathionine beta-synthase alter circulating levels of homocysteine and hydrogen sulfide in mice. Eur J Pharmacol 650:86–93

    Article  PubMed  CAS  Google Scholar 

  35. Cheng Y, Ndisang JF, Tang G et al (2004) Hydrogen sulfide-induced relaxation of resistance mesenteric artery beds of rats. Am J Physiol Heart Circ Physiol 287:H2316–H2323

    Article  PubMed  CAS  Google Scholar 

  36. Li L, Bhatia M, Zhu YZ et al (2005) Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse. FASEB J 19:1196–1198

    PubMed  CAS  Google Scholar 

  37. Szabo C (2007) Hydrogen sulphide and its therapeutic potential. Nat Rev Drug Discov 6:917–935

    Article  PubMed  CAS  Google Scholar 

  38. Qingyou Z, Junbao D, Weijin Z et al (2004) Impact of hydrogen sulfide on carbon monoxide/heme oxygenase pathway in the pathogenesis of hypoxic pulmonary hypertension. Biochem Biophys Res Commun 317:30–37

    Article  PubMed  Google Scholar 

  39. Pan TT, Feng ZN, Lee SW et al (2006) Endogenous hydrogen sulfide contributes to the cardioprotection by metabolic inhibition preconditioning in the rat ventricular myocytes. J Mol Cell Cardiol 40:119–130

    Article  PubMed  CAS  Google Scholar 

  40. Fiorucci S, Antonelli E, Distrutti E et al (2005) Inhibition of hydrogen sulfide generation contributes to gastric injury caused by anti-inflammatory nonsteroidal drugs. Gastroenterology 129:1210–1224

    Article  PubMed  CAS  Google Scholar 

  41. Morrison ML, Blackwood JE, Lockett SL et al (2008) Surviving blood loss using hydrogen sulfide. J Trauma 65:183–188

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, 77004, USA

    Madhura Kulkarni, Ya Fatou Njie-Mbye, Ikechukwu Okpobiri, Min Zhao & Sunny E. Ohia

  2. Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University, Omaha, NE, 68178, USA

    Catherine A. Opere

Authors
  1. Madhura Kulkarni
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  2. Ya Fatou Njie-Mbye
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  3. Ikechukwu Okpobiri
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  4. Min Zhao
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  5. Catherine A. Opere
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  6. Sunny E. Ohia
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Correspondence to Sunny E. Ohia.

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Kulkarni, M., Njie-Mbye, Y.F., Okpobiri, I. et al. Endogenous Production of Hydrogen Sulfide in Isolated Bovine Eye. Neurochem Res 36, 1540–1545 (2011). https://doi.org/10.1007/s11064-011-0482-6

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  • DOI: https://doi.org/10.1007/s11064-011-0482-6

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