Forum: therapeutic applications of reactive oxygen and nitrogen species in human disease
Biological chemistry and clinical potential of S-nitrosothiols

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Abstract

S-Nitrosothiols are endogenous metabolites of nitric oxide that have been detected in extra- and intracellular spaces. Many biological functions of S-nitrosothiols have been described that can be categorized as being due to one or more of the following: (i) nitric oxide release, (ii) transnitrosation, (iii) S-thiolation, and (iv) direct action. This emphasizes the fact that S-nitrosothiols are more than simply nitric oxide donors. Many of the biological functions that have been described for S-nitrosothiols have clinical correlates. This review describes the biological chemistry, biological actions, and clinical potential of these compounds.

Introduction

S-Nitrosothiols are compounds with the generic structure R-SNO. Older, chemical, literature refers to these compounds as thionitrites, but the name ‘S-nitrosothiol’ is now more popular and will be used in this review. Nitrosothiols were first synthesized as early as 1840 [1], and were used in biomedical research in the 1970s and 1980s. As is true for many aspects of nitric oxide biology, the chemistry of S-nitrosothiols, which was sporadically, yet expertly, examined by aficionados for many years, is now directly relevant to the biology of vascular homeostasis, neurotransmission and inflammation.

Section snippets

Synthesis

Most S-nitrosothiols can be synthesized from the reaction between parent thiol and acidified nitrite (, , where RSH represents a thiol and RSNO an S-nitrosothiol). HNO2+H+→NO++H2O RSH+NO+→RSNO+H+ Acidification of a mixture of thiol and sodium nitrite results in the development of color, indicative of S-nitrosothiol formation. The color is usually in the orange-red region, however there are exceptions. For example S-nitroso-N-acetyl penicillamine (SNAP) is purple/green. As many biologically

Biological functions of S-nitrosothiols

Any discussion of the roles of S-nitrosothiols in vivo can be divided into two major concepts: (i) How do exogenously added S-nitrosothiols affect cellular functions?, and (ii) do biological systems use endogenous S-nitrosothiols to control biological responses?

The biological activities of S-nitrosothiols were realized before the landmark discovery that nitric oxide was an endogenously generated molecule [42], [43]. Data obtained using S-nitrosothiols contributed to discerning the identity of

Concluding remarks

S-Nitrosothiols are endogenous compounds that appear to play a role in signal transduction and stress responses. In addition, these compounds have a multitude of pharmacological effects, many of which have immediate clinical corollaries. The development of new bioactive compounds and the development of methodologies to examine both endogenous and exogenous S-nitrosothiols are the driving forces that will no doubt propel these multifaceted agents into the clinical arena.

Acknowledgements

The author would like to thank Drs. B. Kalyanaraman, Victor Darley-Usmar, Ravinder Singh, Eugene Konorev, and Rakesh Patel for insightful and stimulating discussions on the subject of S-nitrosothiols. The author would also like to acknowledge the support of the National Institutes of Health grants GM55792 and RR01008.

References (104)

  • R.P. Patel et al.

    Biochemical characterization of human S-nitrosohemoglobinEffects on oxygen binding and and transnitrosation

    J. Biol. Chem.

    (1999)
  • D.J. Meyer et al.

    Kinetics and equilibria of S-nitrosothiol-thiol exchange between glutathione, cysteine, penicillamines and serum albumin

    FEBS Lett.

    (1994)
  • J.W. Park

    Reaction of S-nitrosoglutathione with sulfhydryl groups in protein

    Biochem. Biophys. Res. Commun.

    (1988)
  • D.R. Arnelle et al.

    NO+, NO, and NO− donation by S-nitrosothiolsimplications for regulation of physiological functions by S-nitrosylation and acceleration of disulfide formation

    Arch. Biochem. Biophys.

    (1995)
  • N. Hogg et al.

    The role of glutathione in the transport and catabolism of nitric oxide

    FEBS Lett.

    (1996)
  • Y. Ji et al.

    S-Nitrosylation and S-glutathiolation of protein sulfhydryls by S-nitrosoglutathione

    Arch. Biochem. Biophys.

    (1999)
  • S. Mohr et al.

    Nitric oxide-induced S-glutathionylation and inactivation of glyceraldehyde-3-phosphate dehydrogenase

    J. Biol. Chem.

    (1999)
  • C.M. Padgett et al.

    Cellular responses to nitric oxide—role of protein S-thiolation/dethiolation

    Arch. Biochem. Biophys.

    (1998)
  • J.M. Fukuto et al.

    Conversion of nitroxyl (HNO) to nitric oxide (NO) in biological systemsthe role of physiological oxidants and relevence to the biological activity of HNO

    Biochem. Biophys. Res. Commun.

    (1993)
  • T. Turk et al.

    Oxidation of dithiothreitol during turnover of nitric oxide reductaseevidence for generation of nitroxyl with the enzyme from paracoccus denitrificans

    Biochem. Biophys. Res. Commun.

    (1992)
  • S.C. Askew et al.

    Chemical mechanisms underlying the vasodilator and platelet anti-aggregating properties of S-nitroso-N-acetyl-DL-penicillamine and S-nitrosoglutathione

    Bioorg. Med. Chem.

    (1995)
  • D. Jourd’heuil et al.

    Effect of superoxide dismutase on the stability of S-nitrosothiols

    Arch. Biochem. Biophys.

    (1999)
  • L.J. Ignarro et al.

    Possible involvement of S-nitrosothiols in the activation of guanylate cyclase by nitroso compounds

    FEBS Lett.

    (1980)
  • E.M. Brendeford et al.

    Nitric oxide (NO) disrupts specific DNA binding of the transcription factor c-Myb in vitro

    FEBS Lett.

    (1998)
  • M.V. Catani et al.

    Inhibition of clotting factor xiii activity by nitric oxide

    Biochem. Biophys. Res. Commun.

    (1998)
  • A.G. Clark et al.

    Inhibition of glutathione S-transferases from rat liver by S-nitroso-L-glutathione

    Biochem. Pharmacol.

    (1988)
  • J. Li et al.

    Nitric oxide reversibly inhibits seven members of the caspase family via S-nitrosylation

    Biochem. Biophys. Res. Commun.

    (1997)
  • A. Hausladen et al.

    Nitrosative stressactivation of the transcription factor OxyR

    Cell

    (1996)
  • N. Hogg et al.

    Inhibition of low-density lipoprotein oxidation by nitric oxide. Potential role in atherogenesis

    FEBS Lett.

    (1993)
  • H. Rubbo et al.

    Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives

    J. Biol. Chem.

    (1994)
  • W. Chamulitrat

    Nitric oxide inhibited peroxyl and alkoxyl radical formation with concomitant protection against oxidant injury in intestinal epithelial cells

    Arch. Biochem. Biophys.

    (1998)
  • H.H. Gutierrez et al.

    Nitric oxide regulation of superoxide-dependent lung injuryoxidant-protective actions of endogenously produced and exogenously administered nitric oxide

    Free Radic. Biol. Med.

    (1996)
  • A.T. Struck et al.

    Nitric oxide donor compounds inhibit the toxicity of oxidized low-density lipoprotein to endothelial cells

    FEBS Lett.

    (1995)
  • C. Bouton et al.

    Modulation of iron regulatory protein functions. Further insights into the role of nitrogen- and oxygen-derived reactive species

    J. Biol. Chem.

    (1996)
  • J.K. Park et al.

    Fluorometric detection of biological S-nitrosothiols

    Anal. Biochem.

    (1997)
  • S. Pfeiffer et al.

    Electrochemical determination of s-nitrosothiols with a clark-type nitric oxide electrode

    Anal. Biochem.

    (1998)
  • P. Ferranti et al.

    Characterisation of S-nitrosohaemoglobin by mass spectrometry

    FEBS Lett.

    (1997)
  • A. Hirayama et al.

    S-nitrosothiols are stored by platelets and released during platelet-neutrophil interactions

    Nitric Oxide

    (1999)
  • C.M. Howard et al.

    S-nitrosoglutathione/glutathione disulphide/Cu2+-dependent stimulation of l-arginine transport in human platelets

    Thromb. Res.

    (1998)
  • A. de Belder et al.

    Treatment of HELLP syndrome with nitric oxide donor

    Lancet

    (1995)
  • E.A. Kowaluk et al.

    Tolerance to relaxation in rat aortacomparison of an S-nitrosothiol with nitroglycerin

    Eur. J. Pharmacol.

    (1987)
  • F. Brunner

    Interaction of nitric oxide and endothelin-1 in ischemia/reperfusion injury of rat heart

    J. Mol. Cell. Cardiol.

    (1997)
  • I.S. Ali et al.

    Cardioprotection by activation of NO/cGMP pathway after cardioplegic arrest and 8-hour storage

    Ann. Thorac. Surg.

    (1998)
  • S. Oae et al.

    Organic thionitrites and related substances

    Organic Preparations and Procedures International

    (1983)
  • Field, L.; Dilts, R. V.; Ravichandran, R.; Lanhert, P. G.; Carnahan, P. G. J. Chem. Soc. Chem. Commun....
  • T.W. Hart

    Some observations concerning the S-nitroso and S-phenylsulphonyl derivatives of L-cysteine and glutathione

    Tetrahedron Lett.

    (1985)
  • Oae, S.; Fukushima, D.; Kim, Y. H. Novel method of activating thiols by their conversion into thionitrites with...
  • D.A. Wink et al.

    Reaction kinetics for nitrosation of cysteine and glutathione in aerobic nitric oxide solutions at neutral pH. Insights into the fate and physiological effects of intermediates generated in the NO/O2 reaction

    Chem. Res. Toxicol.

    (1994)
  • D.J. Sexton et al.

    Visible light photochemical release of nitric oxide from S-nitrosoglutathionepotential photochemotherapeutic applications

    Photochem. Photobiol.

    (1994)
  • Askew, S. C.; Barnett, D. J.; McAninly, J.; Williams, D. L. H. Catalysis by Cu2+ of nitric oxide release from...
  • Cited by (0)

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    Neil Hogg is an Associate Professor in the Biophysics Research Institute of the Medical College of Wisconsin, Milwaukee. He received his Ph.D. in 1993 from the University of Essex, Colchester, UK, under the joint supervision of Dr. Mike Wilson (University of Essex) and Dr. Victor Darley-Usmar (Wellcome Research Laboratories, Beckenham, Kent, UK). Upon hearing the news that Mike Holmgren had become head coach of the Green Bay Packers he headed to Milwaukee to work as a postdoc’ for Dr. Raman Kalyanaraman, and became an Assistant Professor in 1997. His current interests include the role of S-nitrosothiols in biological systems, the biological chemistry of peroxynitrite, the antioxidant behavior of nitric oxide, and the formation of superoxide by nitric oxide synthase isoforms. Despite this year’s 8 and 8 record, he has no plans to move to Seattle.

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