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S-Nitrosothiols: Correlation of Biological Chemistry with Physiological Actions

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Biochemical, Pharmacological, and Clinical Aspects of Nitric Oxide

Abstract

The reactivity of thionitritrites (RS-NOs) has been well-appreciated by synthetic organic chemists since the turn of the twentieth century (1). These compounds have more recently captured the attention of biologists in several different lines of research: the study of the antimicrobial effects of nitrites (2), the biotransformation of organic nitrates (3), and the identification of endothelium derived relaxing factor (EDRF)(4). In each of these areas, S-nitrosothiols have been proposed as biological mediators; yet there is little consensus on their functions. Moreover, the importance of RS-NO in the metabolism of organic nitrates, their role in the prevention of organic nitrate tolerance, and the contribution of RS-NOs to the biological activities of EDRF, remain issues engendering active controversy. Unfortunately, many of these disputes are provoked by erroneous dogma on the mechanism(s) of synthesis, action and decomposition of various RS-NO. These problems are further compounded by extrapolation from the pharmacological effects of exemplary RS-NO such as S-nitroso-cysteine, to the molecular RS-NO class in general.

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Reference

  1. Oae S, Shinhama K (1983) Organic thionitrites and related substances. Organic Preparations and Procedures 15:165–198.

    Article  CAS  Google Scholar 

  2. Morris SL, Hansen JN (1981) Inhibition of Bacillus cereus spore outgrowth by covalent modifications of a sulfhydryl group by nitrosothiol and iodoacetate. J Bacteriol 148:465–471.

    PubMed  CAS  Google Scholar 

  3. Ignarro LJ, Lippton H, Edwards JC, Baricos WH, Hyman AL, Kadowitz PH, Gruetter CA (1981) Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: Evidence for the involvement of S-nitrosothiols as active intermediates. J Pharm Exp Ther 218:739–749.

    CAS  Google Scholar 

  4. Myers PR, Minor RL, Guerra R, Bates JN, Harrison DG (1990) Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble Snitrosocysteine than nitric oxide. Nature; 345:161–163.

    Article  PubMed  CAS  Google Scholar 

  5. Stamler JS, Simon DI, Osborne JA, Mullins ME, Jaraki O, Michel T, Singel DJ, Loscalzo J (1992) S-nitrosylation of proteins with nitric oxide: Synthesis and characterization of biologically active compounds. Proc Natl Acad Sci USA 89:444–448.

    Article  PubMed  CAS  Google Scholar 

  6. Stamler JS (1994) Redox signalling: nitrosylation and related target interactions of nitric oxide. Cell 78:14–20.

    Article  Google Scholar 

  7. Crapo J, Stamler JS (1994) Signalling by non-receptor surface-mediated redox-active biomolecules. J Clin Invest 93:2304.

    Article  PubMed  CAS  Google Scholar 

  8. Tasker HS, Jones HQ (1909) The action of mercaptans on acid chlorides Part II. The acid chlorides of phosphorous, sulfur and nitrogen. J Chem Soc 95:1910.

    Article  CAS  Google Scholar 

  9. McNainly J, Williams DLH (1993) Fate of nitric oxide from the decomposition of S-nitrosothiols. Endothelium,1:141A.

    Article  Google Scholar 

  10. Stamler JS (1994) S-nitrosothiols and the bioregulatory actions of nitrogen oxides through reactions with sulfhydryl groups. Current Topics in Microbiology and Immunology (in press).

    Google Scholar 

  11. Kowaluk EA, Fung HL (1990) Spontaneous liberation of nitric oxide cannot account for in vitro vascular relaxation by S-nitrosothiols. J Pharmacol Exp Ther 255:1256–1264.

    PubMed  CAS  Google Scholar 

  12. Radomski MW, Rees DD, Durta A, Moncada S (1993) S-nitroso-glutathione inhibits platelet activation in vitro and in vivo. Br J Pharmacol 107:745–749.

    Article  Google Scholar 

  13. Arnelle DP, Stamler JS (1994) Liberation of NO+, NO• and NO- from thionitrites: Implications for regulation of physiological functions by S-nitrosylation and acceleration of disulfide formation. Archiv Biochem Biophys (submitted).

    Google Scholar 

  14. Stamler JS, Jaraki O, Osborne, J, Simon DI, Keaney J, Vita J, Singel D, Valeria RC (1992) Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. Proc Natl Acad Sci USA 89:7674–7677.

    Article  PubMed  CAS  Google Scholar 

  15. Stamler JS, Loh E, Roddy MA, Currie KE, Creager MA (1993) Nitric oxide regulates basal systemic and pulmonary vascular resistance in healthy humans. Circulation 89: 2035–2040.

    Article  Google Scholar 

  16. Scharfstein JS, Kearney JF, Slivka A, Welch GN, Vita JA, Stamler JS, Loscalzo J (1994) In vivo transfer of NO between a plasma protein-bound reservoir and low-molecular-weight thiol. J Clin Invest (in press).

    Google Scholar 

  17. Simon DI, Stamler JS, Jaraki O, Keaney J, Osborne JA, Francis SA, Singel DJ, Loscalzo J (1993) Antiplatelet properties of protein S-nitrosothiols derived from nitric oxide and endothelium-derived relaxing factor. Arterioscler and Thrombosis 13:791–799.

    Article  CAS  Google Scholar 

  18. Lipton SA, Choi YB, Pan ZH, Lei SZ, Vincent Chen HS, Sucher NJ, Loscalzo J, Singel DJ, Stamler JS (1993) A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature 364:626–632.

    Article  PubMed  CAS  Google Scholar 

  19. Gaston B, Drazen JM, Jansen A, Sugarbaker DJ, Loscalzo J, Richards W, Stamler JS (1994) Relaxation of human bronchial smooth muscle by S-nitrosothiols in vitro. J Pharm Exp Ther. 268:976–984.

    Google Scholar 

  20. Stamler JS, Singel D, Loscalzo J (1992) Biochemistry of nitric oxide and its redox activated forms. Science 258:1898–1902.

    Article  PubMed  CAS  Google Scholar 

  21. Bolotina VM, Najibi S, Palacino JJ, Pagano PJ, and Cohen RA (1994) Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle. Nature 368, 850–853.

    Article  PubMed  CAS  Google Scholar 

  22. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci, USA 87:1620–1624.

    Article  PubMed  CAS  Google Scholar 

  23. Mohr S, Stamler JS, and Brune B (1994) Mechanism of covalent modification of glyceraldehyde-3-phosphate dehydrogenase at its active site thiol by nitric oxide, peroxynitrite and related nitrosating agents. FEBS Lett. 348, 223–227.

    Article  PubMed  CAS  Google Scholar 

  24. Wu M, Kaminski PM, Fayngersh RP, Groszek LL, Pritchard KA, Kintze TH, Stemerman MB, Wolin MS (1994) Peroxynitrite induces vascular relaxation vai nitric oxide. Am J. Physiol 35: H2108–H2113.

    Google Scholar 

  25. Gaston B, Reilly J, Drazen JM, Fackler J, Ramdev P, Arnelle D, Mullins ME, Sugarbaker DJ, Chee C, Singel DJ, Loscalzo J, and Stamler JS (1993) Endogenous bronchodilator S-nitrosothiols in human air~vays. Proc Natl Acad Sci USA 90, 1095710961.

    Article  Google Scholar 

  26. Rockett KA, Auburn MM, Lowden WB, Clark IA (1991). Killing of Plasmodium falciparum in vivo by nitric oxide derivatives. Infection and Immunity 59: 3280–3283.

    PubMed  CAS  Google Scholar 

  27. Stamler JS, Simon DI, Jaraki O, Osborne JA, Francis S, Mullins M, Singel D, and Loscalzo J (1992) S-nitrosylation of tissue-type plasminogen activator confers vasodilatory and antiplatelet properties on the enzyme. Proc Natl Acad Sci USA 89: 8087–8091.

    Article  PubMed  CAS  Google Scholar 

  28. Gopalakrishna R, Chen ZH, and Gundimeda V (1993) Nitric oxide and nitric oxidegenerating agents induce a reversible inactivation of protein kinase C activity and phorbol ester binding. J Biol Chem 268, 27180–27185.

    PubMed  CAS  Google Scholar 

  29. Duhe RJ, Nielsen MD, Dittman AH, Villacres EC, Chol EJ, and Storm JR (1994). Oxidation of critical cysteine residues of type I adenylyl cyclase by o-lodosobenzoate or nitric oxide reversibly inhibits stimulation by calcium and calmodulin. J Biol Chem 269: 7290–7296.

    PubMed  CAS  Google Scholar 

  30. Lander HM, Sehajpal PK, and Novogrodsyk A. (1993) Nitric oxide signaling: a possible role for G proteins.Immunology 151: 7182–7187.

    CAS  Google Scholar 

  31. Brune B., Dimmler S, Molina y Vedia L, and Lapatina EG (1994) Nitric oxide: a signal for ADP ribosylation of proteins. Life Sci. 54, 61–70.

    Article  PubMed  CAS  Google Scholar 

  32. Grisham MB, Ware K, Gilleland HE, Gilleland LB, Abell CL, Yamada T. (1992) Neutrophil-mediated nitrosamine formation: Role of nitric oxide in rats. Gastroenterology: 103: 1260–1266.

    PubMed  CAS  Google Scholar 

  33. Gaston B, Drazen JM, Loscalzo J, Stamler JS (1994) The biology of nitrogen oxides in the airways.State-of-the-Art. Am J Resp Critical Care Med Dis, 149:538–551.

    CAS  Google Scholar 

  34. Mercer RR, Costa DL, Crapo JD (1993). Alveolar septal injury from low level exposures to nitric oxide (abstract) Am Rev Respir Dis 147:A385.

    Google Scholar 

  35. Stamler JS, Osborne JA, Jaraki O, Rabbani LE, Mullins M, Singel D, Loscalzo J (1993) Adverse effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen. J Clin Invest 1:308–318.

    Article  Google Scholar 

  36. Malino MR (1990) Hyperhomocyst(e)iremia: a common and easily reversible risk factor for occlusive atherosclerosis. Circulation 81:2004–2006.

    Article  Google Scholar 

  37. Starkebaum G and Harlan JM (1986) Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine. J Clin Invest 77:1370–1376.

    Article  PubMed  CAS  Google Scholar 

  38. Heinecke J, Rosen WH, Suzuki LA, Chait A (1987) The role of sulfur-containing aninocaids in superoxide production and modification of low density lipoprotein by arterial smooth muscle. J. Biol. Chem 262:10098–10103.

    PubMed  CAS  Google Scholar 

  39. Stamler JS, Mendelsohn ME, Amarante P, Smick D, Andon N, Davies PF, Cooke JP1, and Loscalzo J (1989) N-acetylcysteine potentiates platelet inhibition by endotheliumderived relaxing factor. Circ Res 65:789–795.

    Article  PubMed  CAS  Google Scholar 

  40. Cooke JS, Stamler JS, Andon N, Davies PF, Loscalzo J (1990) Flow stimulates endothelial cells to release a nitrovasodilator that is potentiated by reduced thiol. Am J Physiol 28:H804–H812.

    Google Scholar 

  41. Feelisch M, TePoel M, Zamora R, Oeussen A, Moncada S (1994) Understanding the controversy over the identity of EDRF. Nature 368: 62–65.

    Article  PubMed  CAS  Google Scholar 

  42. Selke FW, Myers PR, Bates JN, Harrison DG (1990) Am J Physiol (Heart Circ Physiol) 258:H515–H520).

    Google Scholar 

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Authors and Affiliations

  1. Divisions of Respiratory Medicine and Cardiovascular Medicine, Duke University Medical Center, Durham, NC, 27710, USA

    Jonathan S. Stamler

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  1. Jonathan S. Stamler
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Editors and Affiliations

  1. Israel Institute for Biological Research, Ness-Ziona, Israel

    Ben Avi Weissman , Nahum Allon  & Shlomo Shapira ,  & 

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© 1995 Springer Science+Business Media New York

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Stamler, J.S. (1995). S-Nitrosothiols: Correlation of Biological Chemistry with Physiological Actions. In: Weissman, B.A., Allon, N., Shapira, S. (eds) Biochemical, Pharmacological, and Clinical Aspects of Nitric Oxide. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1903-4_7

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  • DOI: https://doi.org/10.1007/978-1-4615-1903-4_7

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5777-3

  • Online ISBN: 978-1-4615-1903-4

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