s nitrosothiols


Summary: A group of organic sulfur-containing nitrites, alkyl thionitrites. S-Nitrosothiols include compounds such as S-NITROSO-N-ACETYLPENICILLAMINE and S-NITROSOGLUTATHIONE.

Top Publications

  1. Liu L, Yan Y, Zeng M, Zhang J, Hanes M, Ahearn G, et al. Essential roles of S-nitrosothiols in vascular homeostasis and endotoxic shock. Cell. 2004;116:617-28 pubmed
    ..Thus, SNOs regulate innate immune and vascular function, and are cleared actively to ameliorate nitrosative stress. Nitrosylation of cysteine thiols is a critical mechanism of NO function in both health and disease. ..
  2. Liu L, Hausladen A, Zeng M, Que L, Heitman J, Stamler J. A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans. Nature. 2001;410:490-4 pubmed
    ..We conclude that GSNO reductase is evolutionarily conserved from bacteria to humans, is critical for SNO homeostasis, and protects against nitrosative stress. ..
  3. Tannenbaum S, White F. Regulation and specificity of S-nitrosylation and denitrosylation. ACS Chem Biol. 2006;1:615-8 pubmed
    ..A paper in this issue of the journal dissects the regulatory system involved in SNO of caspase-3 and highlights the need for more direct investigations of the complex biological regulation by NO signaling. ..
  4. Huang B, Chen C. An ascorbate-dependent artifact that interferes with the interpretation of the biotin switch assay. Free Radic Biol Med. 2006;41:562-7 pubmed
    ..Ascorbate treatment can interfere with the interpretation of the data. Hence, care should be taken when this method is used. ..
  5. Lipton S, Choi Y, Takahashi H, Zhang D, Li W, Godzik A, et al. Cysteine regulation of protein function--as exemplified by NMDA-receptor modulation. Trends Neurosci. 2002;25:474-80 pubmed
    ..This article reviews the basis for these molecular cysteine switches, drawing on the NMDA receptor as an exemplary protein, and proposes a molecular model for the action of S-nitrosylation based on recently derived crystal structures. ..
  6. Gaston B, Sears S, Woods J, Hunt J, Ponaman M, McMahon T, et al. Bronchodilator S-nitrosothiol deficiency in asthmatic respiratory failure. Lancet. 1998;351:1317-9 pubmed
    ..This is the first reported deficiency of an endogenous bronchodilator in the human asthmatic airway lining fluid. We suggest that S-nitrosothiol metabolism may be a target for the development of new asthma therapies. ..
  7. Santhanam L, Gucek M, Brown T, Mansharamani M, Ryoo S, Lemmon C, et al. Selective fluorescent labeling of S-nitrosothiols (S-FLOS): a novel method for studying S-nitrosation. Nitric Oxide. 2008;19:295-302 pubmed publisher
    ..This S-FLOS method offers detection, identification and quantification of S-nitrosated proteins, with the potential for site-specific identification of nitrosation events. ..
  8. Greco T, Hodara R, Parastatidis I, Heijnen H, Dennehy M, Liebler D, et al. Identification of S-nitrosylation motifs by site-specific mapping of the S-nitrosocysteine proteome in human vascular smooth muscle cells. Proc Natl Acad Sci U S A. 2006;103:7420-5 pubmed
    ..Interestingly, seven of the 18 proteins identified are localized within the ER/Golgi complex, suggesting a role for S-nitrosylation in membrane trafficking and ER stress response in vascular smooth muscle. ..
  9. Hogg N. The biochemistry and physiology of S-nitrosothiols. Annu Rev Pharmacol Toxicol. 2002;42:585-600 pubmed

More Information


  1. Gow A, Farkouh C, Munson D, Posencheg M, Ischiropoulos H. Biological significance of nitric oxide-mediated protein modifications. Am J Physiol Lung Cell Mol Physiol. 2004;287:L262-8 pubmed
    ..It is the purpose of this review to examine the possibility that these modifications may play a role in NO-mediated signaling. ..
  2. Hoffmann J, Dimmeler S, Haendeler J. Shear stress increases the amount of S-nitrosylated molecules in endothelial cells: important role for signal transduction. FEBS Lett. 2003;551:153-8 pubmed
    ..These data suggest that long term exposure to shear stress exerts its different atheroprotective effects at least in part via increased S-nitrosylation of specific signaling proteins. ..
  3. Dahm C, Moore K, Murphy M. Persistent S-nitrosation of complex I and other mitochondrial membrane proteins by S-nitrosothiols but not nitric oxide or peroxynitrite: implications for the interaction of nitric oxide with mitochondria. J Biol Chem. 2006;281:10056-65 pubmed
    ..These findings point to a significant role for complex I S-nitrosation and consequent dysfunction during nitrosative stress in disorders such as Parkinson disease and sepsis. ..
  4. Paige J, Xu G, Stancevic B, Jaffrey S. Nitrosothiol reactivity profiling identifies S-nitrosylated proteins with unexpected stability. Chem Biol. 2008;15:1307-16 pubmed publisher
    ..Taken together, our data identify a class of NO targets that form stable nitrosothiols in the cell and are likely to mediate the persistent cellular effects of NO. ..
  5. Benhar M, Forrester M, Hess D, Stamler J. Regulated protein denitrosylation by cytosolic and mitochondrial thioredoxins. Science. 2008;320:1050-4 pubmed publisher
    ..Thus, specific enzymatic mechanisms may regulate basal and stimulus-induced denitrosylation in mammalian cells. ..
  6. Schonhoff C, Matsuoka M, Tummala H, Johnson M, ESTEVEZ A, Wu R, et al. S-nitrosothiol depletion in amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2006;103:2404-9 pubmed
    ..SNO donor compounds may provide new therapeutic options for diseases such as ALS that are associated with deficient S-nitrosylation. ..
  7. Zhang Y, Hogg N. S-Nitrosothiols: cellular formation and transport. Free Radic Biol Med. 2005;38:831-8 pubmed
  8. Jaffrey S, Erdjument Bromage H, Ferris C, Tempst P, Snyder S. Protein S-nitrosylation: a physiological signal for neuronal nitric oxide. Nat Cell Biol. 2001;3:193-7 pubmed
    ..Targets of NO include metabolic, structural and signalling proteins that may be effectors for neuronally generated NO. These findings establish protein S-nitrosylation as a physiological signalling mechanism for nNOS. ..
  9. Jaffrey S, Fang M, Snyder S. Nitrosopeptide mapping: a novel methodology reveals s-nitrosylation of dexras1 on a single cysteine residue. Chem Biol. 2002;9:1329-35 pubmed
    ..Mutagenesis of Cys11 abolished the effect of NO donors on Dexras1, implicating this residue in the NO-mediated activation of Dexras1...
  10. Palmer L, Gaston B. S-nitrosothiol assays that avoid the use of iodine. Methods Enzymol. 2008;440:157-76 pubmed publisher
    ..Each assay, however, has limitations and should be quantitatively complemented by separate assays. Continued improvement in assays will facilitate improved understanding of S-nitrosylation signaling. ..
  11. Gaston B, Singel D, Doctor A, Stamler J. S-nitrosothiol signaling in respiratory biology. Am J Respir Crit Care Med. 2006;173:1186-93 pubmed
    ..Derangements in SNO signaling are implicated in many disorders relevant to pulmonary and critical care medicine, including apnea, hypoxemia, pulmonary hypertension, asthma, cystic fibrosis, pneumonia, and septic shock. ..
  12. Iwakiri Y, Satoh A, Chatterjee S, Toomre D, Chalouni C, Fulton D, et al. Nitric oxide synthase generates nitric oxide locally to regulate compartmentalized protein S-nitrosylation and protein trafficking. Proc Natl Acad Sci U S A. 2006;103:19777-82 pubmed
    ..These data indicate that local NOS action generates organelle-specific protein S-nitrosylation reactions that can regulate intracellular transport processes. ..
  13. Que L, Liu L, Yan Y, Whitehead G, Gavett S, Schwartz D, et al. Protection from experimental asthma by an endogenous bronchodilator. Science. 2005;308:1618-21 pubmed
    ..Our results indicate that endogenous SNOs, governed by GSNOR, are critical regulators of airway responsivity and may provide new therapeutic approaches to asthma. ..
  14. Whalen E, Foster M, Matsumoto A, Ozawa K, Violin J, Que L, et al. Regulation of beta-adrenergic receptor signaling by S-nitrosylation of G-protein-coupled receptor kinase 2. Cell. 2007;129:511-22 pubmed
    ..Cys340 of GRK2 is identified as a principal locus of inhibition by S-nitrosylation. Our studies thus reveal a central molecular mechanism through which GPCR signaling is regulated...
  15. Lancaster J, Gaston B. NO and nitrosothiols: spatial confinement and free diffusion. Am J Physiol Lung Cell Mol Physiol. 2004;287:L465-6 pubmed
  16. Marshall H, Stamler J. Inhibition of NF-kappa B by S-nitrosylation. Biochemistry. 2001;40:1688-93 pubmed
    ..Further, an increase in S-nitrosylated p50 was detected in cells, and the level was modulated by TNFalpha. Taken together, these data suggest that S-nitrosylation of p50 is a physiological mechanism of NF-kappaB regulation. ..
  17. Nadtochiy S, Burwell L, Ingraham C, Spencer C, Friedman A, Pinkert C, et al. In vivo cardioprotection by S-nitroso-2-mercaptopropionyl glycine. J Mol Cell Cardiol. 2009;46:960-8 pubmed publisher
    ..Overall, these results are consistent with a role for mitochondrial S-nitrosation and complex I inhibition in the cardioprotective mechanism of IPC and SNO-MPG in vivo. ..
  18. Prime T, Blaikie F, Evans C, Nadtochiy S, James A, Dahm C, et al. A mitochondria-targeted S-nitrosothiol modulates respiration, nitrosates thiols, and protects against ischemia-reperfusion injury. Proc Natl Acad Sci U S A. 2009;106:10764-9 pubmed publisher
    ..These results support the idea that selectively targeting NO(*) donors to mitochondria is an effective strategy to reversibly modulate respiration and to protect mitochondria against ischemia-reperfusion injury...
  19. Zhang Y, Hogg N. Formation and stability of S-nitrosothiols in RAW 264.7 cells. Am J Physiol Lung Cell Mol Physiol. 2004;287:L467-74 pubmed
    ..To achieve intracellular localization of the nitrosation reaction, mechanisms must be invoked that do not involve the formation of nitric oxide as an intermediate. ..
  20. Li S, Whorton A. Functional characterization of two S-nitroso-L-cysteine transporters, which mediate movement of NO equivalents into vascular cells. Am J Physiol Cell Physiol. 2007;292:C1263-71 pubmed
    ..The mechanism requires transnitrosylation from S-nitrosoalbumin to free cysteine and activity of system L transporters, thereby providing a unique pathway for cellular responses to S-nitrosoalbumin. ..
  21. Laver J, Stevanin T, Read R. Chemiluminescence quantification of NO and its derivatives in liquid samples. Methods Enzymol. 2008;436:113-27 pubmed publisher
    ..They also allow us to distinguish between the various products that may be generated when NO reacts with molecules in complex biological samples such as cell lysates and supernatants. ..
  22. Wang X, Kettenhofen N, Shiva S, Hogg N, Gladwin M. Copper dependence of the biotin switch assay: modified assay for measuring cellular and blood nitrosated proteins. Free Radic Biol Med. 2008;44:1362-72 pubmed publisher
    ..The addition of copper to ascorbate allows for a simple assay modification that dramatically increases sensitivity while maintaining specificity. ..
  23. Broniowska K, Zhang Y, Hogg N. Requirement of transmembrane transport for S-nitrosocysteine-dependent modification of intracellular thiols. J Biol Chem. 2006;281:33835-41 pubmed
  24. Tullett J, Rees D, Shuker D, Gescher A. Lack of correlation between the observed stability and pharmacological properties of S-nitroso derivatives of glutathione and cysteine-related peptides. Biochem Pharmacol. 2001;62:1239-47 pubmed
    ..It is apparent that the potency of an RSNO in a physiological situation will depend on the concentration of the compound present, the presence of trace metal ions such as copper, and the occurrence of transnitrosation reactions. ..
  25. Reynaert N, Ckless K, Korn S, Vos N, Guala A, Wouters E, et al. Nitric oxide represses inhibitory kappaB kinase through S-nitrosylation. Proc Natl Acad Sci U S A. 2004;101:8945-50 pubmed
    ..Collectively, our findings demonstrate that IKKbeta is an important target for the redox regulation of NF-kappaB by endogenous or exogenous NO, providing an additional mechanism for its antiinflammatory properties. ..
  26. Grennan A. Protein S-nitrosylation: potential targets and roles in signal transduction. Plant Physiol. 2007;144:1237-9 pubmed
  27. Megson I, Sogo N, Mazzei F, Butler A, Walton J, Webb D. Inhibition of human platelet aggregation by a novel S-nitrosothiol is abolished by haemoglobin and red blood cells in vitro: implications for anti-thrombotic therapy. Br J Pharmacol. 2000;131:1391-8 pubmed
    ..5. These studies suggest that scavenging of NO by haemoglobin in blood might limit the therapeutic application of S-nitrosothiols as anti-platelet agents. ..
  28. Lopez Sanchez L, Muntane J, De la Mata M, Rodriguez Ariza A. Unraveling the S-nitrosoproteome: tools and strategies. Proteomics. 2009;9:808-18 pubmed publisher
    ..The development of new analytical methods and strategies over the past several years now allows us to investigate the nitrosoproteome on a global scale. ..
  29. Madej E, Folkes L, Wardman P, Czapski G, Goldstein S. Thiyl radicals react with nitric oxide to form S-nitrosothiols with rate constants near the diffusion-controlled limit. Free Radic Biol Med. 2008;44:2013-8 pubmed publisher
    ..These rate constants imply that formation of S-nitrosothiols in biological systems from the combination of thiyl radicals with nitric oxide is much more likely than claimed by Hofstetter et al. ..
  30. Timerghazin Q, Peslherbe G, English A. Structure and stability of HSNO, the simplest S-nitrosothiol. Phys Chem Chem Phys. 2008;10:1532-9 pubmed publisher
    ..Previous quantum-chemical data on RSNOs are reexamined based on the new insight into the SNO electronic structure obtained from the present high-level calculations on HSNO. ..
  31. Deljanin Ilic M, Ilic S, Lazarevic G, Kocic G, Pavlovic R, Stefanovic V. Impact of interval versus steady state exercise on nitric oxide production in patients with left ventricular dysfunction. Acta Cardiol. 2009;64:219-24 pubmed
  32. Kadekaro M, Su G, Chu R, Lei Y, Li J, Fang L. Effects of nitric oxide on expressions of nitrosocysteine and calcium-activated potassium channels in the supraoptic nuclei and neural lobe of dehydrated rats. Neurosci Lett. 2007;411:117-22 pubmed
    ..Our results indicate that NO signaling cascade may control the expression of BK channels through the regulation of nitrosocysteine in SON and neural lobe of rats during osmotic regulation. ..
  33. Chen Y, Huang Y, Khoo K, Meng T. Mass spectrometry-based analyses for identifying and characterizing S-nitrosylation of protein tyrosine phosphatases. Methods. 2007;42:243-9 pubmed
    ..Thus, the methods introduced in this study provide direct evidence to prove the direct link between S-nitrosylation of the catalytic Cys residue and reversible inactivation of PTPs. ..
  34. Ckless K, Reynaert N, Taatjes D, Lounsbury K, van Der Vliet A, Janssen Heininger Y. In situ detection and visualization of S-nitrosylated proteins following chemical derivatization: identification of Ran GTPase as a target for S-nitrosylation. Nitric Oxide. 2004;11:216-27 pubmed
  35. Srivastava S, Dixit B, Ramana K, Chandra A, Chandra D, Zacarias A, et al. Structural and kinetic modifications of aldose reductase by S-nitrosothiols. Biochem J. 2001;358:111-8 pubmed
    ..Our observations also suggest the general possibility that transnitrosation reactions can generate both nitrosated and thiolated products, leading to non-unique changes in protein structure and function. ..
  36. Bonaventura C, Godette G, Ferruzzi G, Tesh S, Stevens R, Henkens R. Responses of normal and sickle cell hemoglobin to S-nitroscysteine: implications for therapeutic applications of NO in treatment of sickle cell disease. Biophys Chem. 2002;98:165-81 pubmed
    ..S-nitrosation is thus shown to have an effect similar to that reported for other SH-group modifications of Hb S, in which R-state stabilization opposes Hb S aggregation. ..
  37. Zaman K, Carraro S, Doherty J, Henderson E, Lendermon E, Liu L, et al. S-nitrosylating agents: a novel class of compounds that increase cystic fibrosis transmembrane conductance regulator expression and maturation in epithelial cells. Mol Pharmacol. 2006;70:1435-42 pubmed
    ..They also suggest that the effect of GSNO is dependent on Csp and on intracellular SNO trafficking. We speculate that these data will be of relevance to the development of NO donor-based therapies for CF. ..
  38. Ogulener N, Ergun Y. A putative role for S-nitrosoglutathione as the source of nitric oxide in photorelaxation of the mouse gastric fundus. Eur J Pharmacol. 2002;450:267-75 pubmed
    ..These results suggest that S-nitrosoglutathione may, at least in part, be the putative S-nitrosothiol, which is converted to NO in response to UV irradiation in mouse gastric fundus strips...
  39. Pereira E, Bertolami M, Faludi A, Salem M, Bersch D, Abdalla D. Effects of simvastatin and L-arginine on vasodilation, nitric oxide metabolites and endogenous NOS inhibitors in hypercholesterolemic subjects. Free Radic Res. 2003;37:529-36 pubmed
    ..Our data showed that simvastatin reduced the plasma concentrations of NOx and RSNO without affecting either the levels of ADMA or endothelium-dependent vasodilation in hypercholesterolemia. ..
  40. Foster M, Pawloski J, Singel D, Stamler J. Role of circulating S-nitrosothiols in control of blood pressure. Hypertension. 2005;45:15-7 pubmed
  41. Forrester M, Thompson J, Foster M, Nogueira L, Moseley M, Stamler J. Proteomic analysis of S-nitrosylation and denitrosylation by resin-assisted capture. Nat Biotechnol. 2009;27:557-9 pubmed publisher
    ..This methodology is readily adapted to analyzing diverse cysteine-based protein modifications, including S-acylation. ..
  42. Moriondo A, Rispoli G. The contribution of cationic conductances to the potential of rod photoreceptors. Eur Biophys J. 2010;39:889-902 pubmed publisher
    ..The latter kinetics was instead accelerated by the hyperpolarisation-activated, non-selective current (I (h)) and I (Ca). Blockade of all K(+) currents with external TEA unmasked a I (Ca)-dependent regenerative behaviour. ..
  43. Winyard P, Knight I, Shaw F, Rocks S, Davies C, Eggleton P, et al. Determination of S-nitrosothiols in biological and clinical samples using electron paramagnetic resonance spectrometry with spin trapping. Methods Enzymol. 2008;441:151-60 pubmed publisher
    ..This iron complex mediates the decomposition of RSNO to NO., as well as spin trapping the generated NO.. The resulting spin adduct has a unique EPR signal that can be quantified. ..
  44. Lin J, Steenbergen C, Murphy E, Sun J. Estrogen receptor-beta activation results in S-nitrosylation of proteins involved in cardioprotection. Circulation. 2009;120:245-54 pubmed publisher
  45. Bossy Wetzel E, Talantova M, Lee W, Scholzke M, Harrop A, Mathews E, et al. Crosstalk between nitric oxide and zinc pathways to neuronal cell death involving mitochondrial dysfunction and p38-activated K+ channels. Neuron. 2004;41:351-65 pubmed
    ..Thus, these data establish a new form of crosstalk between NO and Zn2+ apoptotic signal transduction pathways that may contribute to neurodegeneration. ..
  46. Gaston B. Summary: systemic effects of inhaled nitric oxide. Proc Am Thorac Soc. 2006;3:170-2 pubmed
    ..In this article, many of the whole-animal studies regarding the systemic effects of inhaled NO are reviewed in the context of this emerging understanding of the complexities of NO biochemistry. ..
  47. Al Sa doni H, Ferro A. S-nitrosothiols as nitric oxide-donors: chemistry, biology and possible future therapeutic applications. Curr Med Chem. 2004;11:2679-90 pubmed
    ..In this review, we examine in detail the biological functions of S-nitrosothiols, as well as the chemical properties and biomedical applications of these compounds. ..
  48. Masters K, Lipke E, Rice E, Liel M, Myler H, Zygourakis C, et al. Nitric oxide-generating hydrogels inhibit neointima formation. J Biomater Sci Polym Ed. 2005;16:659-72 pubmed
    ..Localized delivery of NO from hydrogels containing Cys-NO inhibited neointima formation in a rat balloon-injury model by approximately 75% at 14 days. ..
  49. Johnson M, Macdonald T, Mannick J, Conaway M, Gaston B. Accelerated s-nitrosothiol breakdown by amyotrophic lateral sclerosis mutant copper,zinc-superoxide dismutase. J Biol Chem. 2001;276:39872-8 pubmed
    ..We have identified a potentially toxic gain of function of two common FALS mutations that may contribute to neurodegeneration in FALS. ..
  50. Kim Shapiro D, Patel R, Schechter A, Gladwin M, Cannon R, Hogg N. How do red blood cells dilate blood vessels?--Reply. Circ Res. 2004;95:e10 pubmed
  51. Ng C, Najbar Kaszkiel A, Li C. Role of copper in the relaxant action of S-nitrosothiols in the rat anococcygeus muscle. Clin Exp Pharmacol Physiol. 2003;30:357-61 pubmed
    ..but had no effect on relaxations to SNAP, SNP or EFS. 5. In conclusion, the results indicate that Cu[I], but not Cu[II], may be involved in the relaxant actions of GSNO and SNAP in the rat anococcygeus muscle. ..
  52. Haendeler J. Thioredoxin-1 and posttranslational modifications. Antioxid Redox Signal. 2006;8:1723-8 pubmed
    ..This review focuses on the posttranslational modifications of the active and nonactive cysteines and their contribution for functional regulation of thioredoxin-1. ..
  53. Mauel J, Ransijn A. Leishmania spp.: mechanisms of toxicity of nitrogen oxidation products. Exp Parasitol. 1997;87:98-111 pubmed
    ..These results indicate that several cellular targets may be subject to NO toxicity in Leishmania parasites, including enzymes of glycolysis and respiratory metabolism as well as trans-membrane transport systems...