s nitrosoglutathione


Summary: A sulfur-containing alkyl thionitrite that is one of the NITRIC OXIDE DONORS.

Top Publications

  1. Schrammel A, Gorren A, Schmidt K, Pfeiffer S, Mayer B. S-nitrosation of glutathione by nitric oxide, peroxynitrite, and (*)NO/O(2)(*-). Free Radic Biol Med. 2003;34:1078-88 pubmed
    ..Our results indicate that concerted generation of (*)NO and O(2)(*)(-) may essentially contribute to nitrosative stress in inflammatory diseases. ..
  2. Kaposzta Z, Clifton A, Molloy J, Martin J, Markus H. S-nitrosoglutathione reduces asymptomatic embolization after carotid angioplasty. Circulation. 2002;106:3057-62 pubmed
    ..No cerebrovascular events occurred in the GSNO group. S-nitrosoglutathione was highly effective in rapidly reducing the frequency of embolic signals after endovascular treatment for symptomatic high-grade carotid stenosis. ..
  3. 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. ..
  4. Chiueh C. S-nitrosoglutathione (GSNO) mediates brain response to hypoxia. Pediatr Res. 2002;51:414 pubmed
  5. Foster M, Stamler J. New insights into protein S-nitrosylation. Mitochondria as a model system. J Biol Chem. 2004;279:25891-7 pubmed
    ..Collectively, our results provide new insight into the determinants of S-nitrosothiol levels in subcellular compartments. ..
  6. Pullan S, Gidley M, Jones R, Barrett J, Stevanin T, Read R, et al. Nitric oxide in chemostat-cultured Escherichia coli is sensed by Fnr and other global regulators: unaltered methionine biosynthesis indicates lack of S nitrosation. J Bacteriol. 2007;189:1845-55 pubmed
  7. 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. ..
  8. Khan M, Sekhon B, Giri S, Jatana M, Gilg A, Ayasolla K, et al. S-Nitrosoglutathione reduces inflammation and protects brain against focal cerebral ischemia in a rat model of experimental stroke. J Cereb Blood Flow Metab. 2005;25:177-92 pubmed
    ..That GSNO protects the brain against ischemia/reperfusion injury by modulating NO systems, resulting in a reduction in inflammation and neuronal cell death was documented by the results. ..
  9. He J, Kang H, Yan F, Chen C. The endoplasmic reticulum-related events in S-nitrosoglutathione-induced neurotoxicity in cerebellar granule cells. Brain Res. 2004;1015:25-33 pubmed
    ..These effects indicate that ER is one of the NO targets in GSNO-induced neurotoxicity in cerebellar granule cells besides mitochondria. ..

More Information


  1. Corriveau C, Madara P, Van Dervort A, Tropea M, Wesley R, Danner R. Effects of nitric oxide on chemotaxis and endotoxin-induced interleukin-8 production in human neutrophils. J Infect Dis. 1998;177:116-26 pubmed
    ..009). These data suggest that NO does not directly affect neutrophil chemotaxis but may indirectly alter chemotactic responses by increasing IL-8 production via a cGMP-independent pathway. ..
  2. Prasad R, Giri S, Nath N, Singh I, Singh A. GSNO attenuates EAE disease by S-nitrosylation-mediated modulation of endothelial-monocyte interactions. Glia. 2007;55:65-77 pubmed
    ..These observations suggest that GSNO exerts its protective effects in EAE by inhibition of cellular infiltration into the CNS by S-nitrosylation of p65, thereby modulating NF-kappaB-CAMs pathway in endothelial cells. ..
  3. von Knethen A, Brüne B. Activation of peroxisome proliferator-activated receptor gamma by nitric oxide in monocytes/macrophages down-regulates p47phox and attenuates the respiratory burst. J Immunol. 2002;169:2619-26 pubmed
    ..We conclude that NO participates in controlling the pro- vs anti-inflammatory phenotype of macrophages by modulating PPARgamma. ..
  4. Flatley J, Barrett J, Pullan S, Hughes M, Green J, Poole R. Transcriptional responses of Escherichia coli to S-nitrosoglutathione under defined chemostat conditions reveal major changes in methionine biosynthesis. J Biol Chem. 2005;280:10065-72 pubmed
    ..The data presented here reveal new genes important for nitrosative stress tolerance and demonstrate that methionine biosynthesis is a casualty of nitrosative stress. ..
  5. Kuo Y, Wang F, Jeng S, Huang H, Wei F, Yang K. Nitrosoglutathione modulation of platelet activation and nitric oxide synthase expression in promotion of flap survival after ischemia/reperfusion injury. J Surg Res. 2004;119:92-9 pubmed
    ..This study suggests that GSNO can appropriately donate NO to suppress platelet activation and platelet iNOS induction, resulting in less platelet activation, better blood perfusion, and flap survival after I/R injury. ..
  6. Steffen M, Sarkela T, Gybina A, Steele T, Trasseth N, Kuehl D, et al. Metabolism of S-nitrosoglutathione in intact mitochondria. Biochem J. 2001;356:395-402 pubmed
  7. Zeng H, Spencer N, Hogg N. Metabolism of S-nitrosoglutathione by endothelial cells. Am J Physiol Heart Circ Physiol. 2001;281:H432-9 pubmed
    ..We conclude that the intracellular thiol pool causes the reduction of extracellular disulfides to thiols, which then directly reduce GSNO. ..
  8. Kim S, Huri D, Snyder S. Inducible nitric oxide synthase binds, S-nitrosylates, and activates cyclooxygenase-2. Science. 2005;310:1966-70 pubmed
    ..Selectively disrupting iNOS-COX-2 binding prevented NO-mediated activation of COX-2. This synergistic molecular interaction between two inflammatory systems may inform the development of anti-inflammatory drugs. ..
  9. Hara M, Agrawal N, Kim S, Cascio M, Fujimuro M, Ozeki Y, et al. S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding. Nat Cell Biol. 2005;7:665-74 pubmed
    ..The NO-S-nitrosylation-GAPDH-Siah1 cascade may represent an important molecular mechanism of cytotoxicity. ..
  10. Gaston B, Carver J, Doctor A, Palmer L. S-nitrosylation signaling in cell biology. Mol Interv. 2003;3:253-63 pubmed
    ..These recent insights regarding the bioactivities, molecular signaling pathways, and metabolism of endogenous S-nitrosothiols have suggested several new therapies for disease ranging from cystic fibrosis to pulmonary hypertension. ..
  11. Kaposzta Z, Martin J, Markus H. Switching off embolization from symptomatic carotid plaque using S-nitrosoglutathione. Circulation. 2002;105:1480-4 pubmed
    ..GSNO was highly effective in rapidly reducing the frequency of embolic signals in this patient group. Despite its short administration time and its short half-life, it resulted in therapeutic effects lasting 24 hours. ..
  12. Stevanin T, Ioannidis N, Mills C, Kim S, Hughes M, Poole R. Flavohemoglobin Hmp affords inducible protection for Escherichia coli respiration, catalyzed by cytochromes bo' or bd, from nitric oxide. J Biol Chem. 2000;275:35868-75 pubmed
    ..The results demonstrate the role of Hmp in protecting respiration from NO stress and are discussed in relation to the energy metabolism of E. coli in natural O(2)-depleted environments. ..
  13. Crawford M, Goldberg D. Regulation of the Salmonella typhimurium flavohemoglobin gene. A new pathway for bacterial gene expression in response to nitric oxide. J Biol Chem. 1998;273:34028-32 pubmed
    ..These data unveil a new pathway for NO-dependent gene expression in S. typhimurium. ..
  14. Membrillo Hernandez J, Coopamah M, Channa A, Hughes M, Poole R. A novel mechanism for upregulation of the Escherichia coli K-12 hmp (flavohaemoglobin) gene by the 'NO releaser', S-nitrosoglutathione: nitrosation of homocysteine and modulation of MetR binding to the glyA-hmp intergenic region. Mol Microbiol. 1998;29:1101-12 pubmed
    ..As GSNO and SNP upregulate hmp similarly, the NO released in the former case on reaction with homocysteine cannot be involved in hmp regulation. ..
  15. Savidge T, Newman P, Pothoulakis C, Ruhl A, Neunlist M, Bourreille A, et al. Enteric glia regulate intestinal barrier function and inflammation via release of S-nitrosoglutathione. Gastroenterology. 2007;132:1344-58 pubmed
  16. Duan S, Wan L, Fu W, Pan H, Ding Q, Chen C, et al. Nonlinear cooperation of p53-ING1-induced bax expression and protein S-nitrosylation in GSNO-induced thymocyte apoptosis: a quantitative approach with cross-platform validation. Apoptosis. 2009;14:236-45 pubmed publisher
  17. Jensen D, Belka G. Enzymic denitrosation of 1,3-dimethyl-2-cyano-1-nitrosoguanidine in rat liver cytosol and the fate of the immediate product S-nitrosoglutathione. Biochem Pharmacol. 1997;53:1279-95 pubmed
    ..The fate of the NO moiety consequent to this GSNO catabolism is presently unknown. ..
  18. Ederli L, Reale L, Madeo L, Ferranti F, Gehring C, Fornaciari M, et al. NO release by nitric oxide donors in vitro and in planta. Plant Physiol Biochem. 2009;47:42-8 pubmed publisher
    ..In spite of the different NO release signatures by SNP and NOS in tissue, the NO dependent responses examined were similar, suggesting that there is a critical threshold for the NO response. ..
  19. Lushchak O, Nykorak N, Ohdate T, Inoue Y, Lushchak V. Inactivation of genes encoding superoxide dismutase modifies yeast response to S-nitrosoglutathione-induced stress. Biochemistry (Mosc). 2009;74:445-51 pubmed
    ..A GSNO-induced increase in oxidized glutathione level in the studied yeast strains might account for cell killing by GSNO due to the development of oxidative/nitrosative stress. ..
  20. Fotiou S, Fotiou D, Alamanou A, Deliconstantinos G. Resveratrol activation of nitric oxide synthase in rabbit brain synaptosomes: singlet oxygen (1O2) formation as a causative factor of neurotoxicity. In Vivo. 2010;24:49-53 pubmed
    ..The present study concerning the behavior of resveratrol with respect to its structure and potential prooxidant-antioxidant function provides important new clues as to the role of this fascinating molecule in pathophysiology...
  21. Stepuro I, Adamchuk R, Piletskaya T, Stepuro V, Maskevich S. Ultrasound-induced formation of S-nitrosoglutathione and S-nitrosocysteine in aerobic aqueous solutions of glutathione and cysteine. Biochemistry (Mosc). 2000;65:1385-96 pubmed
    ..The main target for ultrasound-generated oxygen free radicals were cystine residues oxidized to cysteic acid residues. ..
  22. Baker J, Contney S, Singh R, Kalyanaraman B, Gross G, Bosnjak Z. Nitric oxide activates the sarcolemmal K(ATP) channel in normoxic and chronically hypoxic hearts by a cyclic GMP-dependent mechanism. J Mol Cell Cardiol. 2001;33:331-41 pubmed
    ..The effect of ODQ could not be reversed by GSNO. We conclude that NO activates the sarcolemmal K(ATP) channel in normoxic and chronically hypoxic hearts by a cyclic GMP-dependent mechanism. ..
  23. Li J, Liu Z, Tao J. The effects of nitric oxide donors on the sporulation of Eimeria tenella oocysts. Vet Parasitol. 2008;154:336-40 pubmed publisher
    ..At present, the inhibiting mechanism of NO donors on the sporulation of oocysts was still unclear. ..
  24. Nahrevanian H, Farahmand M, Aghighi Z, Assmar M, Amirkhani A. Pharmacological evaluation of anti-leishmanial activity by in vivo nitric oxide modulation in Balb/c mice infected with Leishmania major MRHO/IR/75/ER: an Iranian strain of cutaneous leishmaniasis. Exp Parasitol. 2007;116:233-40 pubmed
    ..An inconsistent relationship was evident between the NO modulation and pathological changes in treated Balb/c mice infected with L. major IR/75. ..
  25. Naseem K, Chirico S, Mohammadi B, Bruckdorfer K. The synergism of hydrogen peroxide with plasma S-nitrosothiols in the inhibition of platelet activation. Biochem J. 1996;318 ( Pt 3):759-66 pubmed
    ..These results suggest a potent synergism of H2O2 with endogenous plasma nitrosothiols that inhibit platelet function through an intracellular mechanism involving guanylate cyclase. ..
  26. Wedel B, Humbert P, Harteneck C, Foerster J, Malkewitz J, Bohme E, et al. Mutation of His-105 in the beta 1 subunit yields a nitric oxide-insensitive form of soluble guanylyl cyclase. Proc Natl Acad Sci U S A. 1994;91:2592-6 pubmed
    ..Thus, the mutation provides a means to inhibit the nitric oxide-sensitive guanylyl cyclase signaling pathway. ..
  27. Jurasz P, Stewart M, Radomski A, Khadour F, Duszyk M, Radomski M. Role of von Willebrand factor in tumour cell-induced platelet aggregation: differential regulation by NO and prostacyclin. Br J Pharmacol. 2001;134:1104-12 pubmed
    ..10. Prostacyclin and NO inhibit TCIPA-sVWF-mediated platelet aggregation. The mechanisms of inhibition of this aggregation by PGI(2) differ from those of NO. ..
  28. Kim J, Kim Y, Lee M. Proteomic characterization of differentially expressed proteins associated with no stress in retinal ganglion cells. BMB Rep. 2009;42:456-61 pubmed
    ..These results suggest that NO stress-induced apoptosis may be associated with the nuclear translocation and accumulation of GAPDH in RGC-5 cells. ..
  29. Wood S, Firoved A, Ornatowski W, Mai T, Deretic V, Timmins G. Nitrosative stress inhibits production of the virulence factor alginate in mucoid Pseudomonas aeruginosa. Free Radic Res. 2007;41:208-15 pubmed
    ..Our data suggest that the lowered levels of innate-immune nitrosative mediators (such as GSNO) in the CF lung exacerbate the effects of mucoid P. aeruginosa, by failing to suppress alginate biosynthesis. ..
  30. Brendeford E, Andersson K, Gabrielsen O. Nitric oxide (NO) disrupts specific DNA binding of the transcription factor c-Myb in vitro. FEBS Lett. 1998;425:52-6 pubmed
    ..This difference in NO sensitivity may influence the regulation of wild type versus AMV v-Myb protein function. ..
  31. Smirnova J, Zhukova L, Witkiewicz Kucharczyk A, Kopera E, Oledzki J, Wysłouch Cieszyńska A, et al. Reaction of the XPA zinc finger with S-nitrosoglutathione. Chem Res Toxicol. 2008;21:386-92 pubmed publisher
    ..In the case of XPA, this may lead to DNA repair inhibition. ..
  32. Lu S, Killoran P, Fang F, Riley L. The global regulator ArcA controls resistance to reactive nitrogen and oxygen intermediates in Salmonella enterica serovar Enteritidis. Infect Immun. 2002;70:451-61 pubmed
    ..enterica serovar Enteritidis to nitrosative and oxidative stress. However, additional genetic loci may contribute to the resistance to RNI/ROI and unusually high virulence for mice of SE2472. ..
  33. Volbracht C, Chua B, Ng C, Bahr B, Hong W, Li P. The critical role of calpain versus caspase activation in excitotoxic injury induced by nitric oxide. J Neurochem. 2005;93:1280-92 pubmed
  34. Jia H, Liu Y, Zhang X, Han L, Du L, Tian Q, et al. Potential oxidative stress of gold nanoparticles by induced-NO releasing in serum. J Am Chem Soc. 2009;131:40-1 pubmed publisher
    ..In this reaction the NO production was catalyzed on the surface of the nanoparticles, and a new bond of Au-thiolate was simultaneously formed. ..
  35. Sadidi M, Geddes T, Kuhn D. S-thiolation of tyrosine hydroxylase by reactive nitrogen species in the presence of cysteine or glutathione. Antioxid Redox Signal. 2005;7:863-9 pubmed
    ..Glutathione disulfide S-oxide, which forms spontaneously in the decomposition of GSNO and which is found in tissue undergoing oxidative stress, may be the species that S-thiolates TH. ..
  36. Watts R, Richardson D. The mechanism of nitrogen monoxide (NO)-mediated iron mobilization from cells. NO intercepts iron before incorporation into ferritin and indirectly mobilizes iron from ferritin in a glutathione-dependent manner. Eur J Biochem. 2002;269:3383-92 pubmed
    ..Based on our results, we propose a model of glucose-dependent NO-mediated Fe mobilization. ..
  37. Choudhry S, Que L, Yang Z, Liu L, Eng C, Kim S, et al. GSNO reductase and beta2-adrenergic receptor gene-gene interaction: bronchodilator responsiveness to albuterol. Pharmacogenet Genomics. 2010;20:351-8 pubmed publisher
    ..Genotyping of GSNOR and beta2AR genes may be useful in identifying Latino individuals, who might benefit from adjuvant therapy for refractory asthma. ..
  38. Pae H, Kim H, Paik Y, Paik S, Kim Y, Oh G, et al. Nitric oxide protects murine embryonic liver cells (BNL CL.2) from cytotoxicity induced by glucose deprivation. Pharmacol Toxicol. 2000;86:140-4 pubmed
    ..Based upon these results, we suggest that nitric oxide may enhance the cell survival of BNL CL.2 cells after glucose deprivation via a guanosine 3',5'-cyclic monophosphate-independent pathway. ..
  39. Rassaf T, Kleinbongard P, Preik M, Dejam A, Gharini P, Lauer T, et al. Plasma nitrosothiols contribute to the systemic vasodilator effects of intravenously applied NO: experimental and clinical Study on the fate of NO in human blood. Circ Res. 2002;91:470-7 pubmed
    ..These findings demonstrate that in humans the pharmacological delivery of NO solutions results in the transport and delivery of NO as RSNOs along the vascular tree. ..
  40. Shi Q, Lou Y. Microsomal glutathione transferase 1 is not S-nitrosylated in rat liver microsomes or in endotoxin challenged rats. Pharmacol Res. 2005;51:303-10 pubmed
    ..Further studies on the novel S-nitrosylable microsomal proteins are also warranted. ..
  41. Aesif S, Janssen Heininger Y, Reynaert N. Protocols for the detection of s-glutathionylated and s-nitrosylated proteins in situ. Methods Enzymol. 2010;474:289-96 pubmed publisher
    ..These techniques can be applied in situ to elucidate which compartments in tissues are affected in diseased states whose underlying pathologies are thought to represent a redox imbalance. ..
  42. Garcia Mata C, Lamattina L. Abscisic acid (ABA) inhibits light-induced stomatal opening through calcium- and nitric oxide-mediated signaling pathways. Nitric Oxide. 2007;17:143-51 pubmed
    ..Results also support that Ca2+ induces the NO production through the activation of a NOS-like activity. ..
  43. Camerini S, Polci M, Restuccia U, Usuelli V, Malgaroli A, Bachi A. A novel approach to identify proteins modified by nitric oxide: the HIS-TAG switch method. J Proteome Res. 2007;6:3224-31 pubmed
    ..We report here a novel strategy, defined His-tag switch, which allows the purification and identification of S-nitrosylated proteins and the unambiguous localization of the modified cysteine residues by mass spectrometry analysis. ..
  44. Cui X, Zhang J, Ma P, Myers D, Goldberg I, Sittler K, et al. cGMP-independent nitric oxide signaling and regulation of the cell cycle. BMC Genomics. 2005;6:151 pubmed
    ..In humans, antiproliferative effects of NO* may rely substantially on cGMP-independent mechanisms. Stress kinase signaling and alterations in mRNA stability appear to be major pathways by which NO* regulates the transcriptome. ..
  45. Seabra A, Fitzpatrick A, Paul J, De Oliveira M, Weller R. Topically applied S-nitrosothiol-containing hydrogels as experimental and pharmacological nitric oxide donors in human skin. Br J Dermatol. 2004;151:977-83 pubmed
    ..At high levels of blood flow, there is a reduction in dermal nitrite, which is presumed to be due to increased blood scavenging. ..
  46. Krezel A, Bal W. Contrasting effects of metal ions on S-nitrosoglutathione, related to coordination equilibria: GSNO decomposition assisted by Ni(II) vs stability Increase in the presence of Zn(II) and Cd(II). Chem Res Toxicol. 2004;17:392-403 pubmed
    ..The Ni(II)-dependent destabilization of GSNO may constitute a novel epigenetic mechanism in nickel carcinogenesis. ..
  47. Fabisiak J, Sedlov A, Kagan V. Quantification of oxidative/nitrosative modification of CYS(34) in human serum albumin using a fluorescence-based SDS-PAGE assay. Antioxid Redox Signal. 2002;4:855-65 pubmed
  48. Chazotte Aubert L, Pluquet O, Hainaut P, Ohshima H. Nitric oxide prevents gamma-radiation-induced cell cycle arrest by impairing p53 function in MCF-7 cells. Biochem Biophys Res Commun. 2001;281:766-71 pubmed
    ..This Bax accumulation, however, was shown to occur via a p53-independent pathway. ..
  49. Gende O. Attenuation of alkalizing effect of thrombin by S-nitrosoglutathione in human platelets. Platelets. 2000;11:199-203 pubmed
    ..As a conclusion, these drugs in addition to the reduction of rise in [Ca2+]i have an inhibitory effect on the alkalizing response induced by thrombin. ..
  50. Albina J, Mastrofrancesco B, Reichner J. Acyl phosphatase activity of NO-inhibited glyceraldehyde-3-phosphate dehydrogenase (GAPDH): a potential mechanism for uncoupling glycolysis from ATP generation in NO-producing cells. Biochem J. 1999;341 ( Pt 1):5-9 pubmed
    ..These cellular alterations could be explained by the uncoupling of glycolytic flux from substrate level phosphorylation by the acyl phosphatase activity of NO-modified GAPDH. ..
  51. Chin T, Chueh S, Tao P. S-Nitrosoglutathione and glutathione act as NMDA receptor agonists in cultured hippocampal neurons. Acta Pharmacol Sin. 2006;27:853-60 pubmed
    ..GSNO and glutathione act as NMDA receptor agonists and, in contrast to hippocampal brain slice, combined pre- and postnatal morphine exposure does not modulate NMDA receptor signaling in the cultured hippocampal neurons. ..
  52. Lancaster J. NO parkin in Parkinson's disease. Science. 2004;304:1905; author reply 1905 pubmed
  53. Adrian K, Skogby M, Friberg L, Mellgren K. The effect of s-nitroso-glutathione on platelet and leukocyte function during experimental extracorporeal circulation. Artif Organs. 2003;27:570-5 pubmed
    ..In this study, no significant effect of GSNO on circulating platelets or leukocytes during experimental extracorporeal circulation could be shown. ..