Abstract
S-Nitrosoglutathione (GSNO) is a very important biomolecule that has crucial functions in many physiological and physiopathological processes. GSNO acts as NO donor and is a candidate for future medicines. This work describes, for the first time, the separation and the detection of GSNO and its decomposition products using capillary electrophoresis coupled to mass spectrometry (CE–MS). The separation was performed in slightly alkaline medium (pH 8.5) under positive-ionization MS detection. The identification of three byproducts of GSNO was formally performed for the first time: oxidized glutathione (GSSG), glutathione sulfinic acid (GSO2H), and glutathione sulfonic acid (GSO3H). GSO2H and GSO3H are known to have important biological activity, including inhibition of the glutathione transferase family of enzymes which are responsible for the elimination of many mutagenic, carcinogenic, and pharmacologically active molecules. We observed, after the ageing of GSNO in the solid state, that the proportion of both GSSG and GSO3H increases whereas that of GSO2H decreases. These results enabled us to propose an oxidation scheme explaining the formation of such products.
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References
Broniowska KA, Diers AR, Hogg N (2013) S-Nitrosoglutathione. Biochim Biophys Acta 1830(5):3173–3181
Williams DLH (1999) The chemistry of S-nitrosothiols. Acc Chem Res 32(10):869–876
Wong PSY, Hyun J, Fukuto JM, Shirota FN, DeMaster EG, Shoeman DW, Nagasawa HT (1998) Reaction between S-nitrosothiols and thiols: Generation of nitroxyl (HNO) and subsequent chemistry. Biochemistry 37(16):5362–5371
Claiborne A, Yeh JI, Mallett TC, Luba J, Crane EJ, Charrier V, Parsonage D (1999) Protein-Sulfenic Acids:Diverse Roles for an Unlikely Player in Enzyme Catalysis and Redox Regulation. Biochemistry 38(47):15407–15416
Giustarini D, Milzani A, Dalle-Donne I, Rossi R (2007) Detection of S-nitrosothiols in biological fluids: A comparison among the most widely applied methodologies. J Chromatogr B 851(1–2):124–139
Wang S, Circu ML, Zhou H, Figeys D, Aw TY, Feng J (2011) Highly sensitive detection of S-nitrosylated proteins by capillary gel electrophoresis with laser induced fluorescence. J Chromatogr A 1218(38):6756–6762
Carru C, Zinellu A, Sotgia S, Marongiu G, Farina MG, Usai MF, Pes GM, Tadolini B, Deiana L (2003) Optimization of the principal parameters for the ultrarapid electrophoretic separation of reduced and oxidized glutathione by capillary electrophoresis. J Chromatogr A 1017(1–2):233–238
Yoo J-W, Acharya G, Lee CH (2009) In vivo evaluation of vaginal films for mucosal delivery of nitric oxide. Biomaterials 30(23–24):3978–3985
Saville B (1958) A scheme for the colorimetric determination of microgram amounts of thiols. Analyst 83(993):670–672
Tsikas D, Raida M, Sandmann J, Rossa S, Forssmann WG, Frolich JC (2000) Electrospray ionization mass spectrometry of low-molecular-mass S-nitroso compounds and their thiols. J Chromatogr B 742(1):99–108
van der Toorn M, Vries MPS, Slebos DJ, de Bruin HG, Abello N, van Oosterhout AJM, Bischoff R, Kauffman HF (2007) Cigarette smoke irreversibly modifies glutathione in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 293(5):L1156–L1162
Staab CA, Alander J, Brandt M, Lengqvist J, Morgenstern R, Grafstrom RC, Hoog JO (2008) Reduction of S-nitrosoglutathione by alcohol dehydrogenase 3 is facilitated by substrate alcohols via direct cofactor recycling and leads to GSH-controlled formation of glutathione transferase inhibitors. Biochem J 413:493–504
Yang CY, Gu ZW, Yang ML, Lin SN, Garcia-Prats AJ, Rogers LK, Welty SE, Smith CV (1999) Selective modification of apoB-100 in the oxidation of low density lipoproteins by myeloperoxidase in vitro. J Lipid Res 40(4):686–698
Lindahl M, Mata-Cabana A, Kieselbach T (2011) The Disulfide Proteome and Other Reactive Cysteine Proteomes: Analysis and Functional Significance. Antioxid Redox Signal 14(12):2581–2641
Lo Conte M, Carroll KS (2012) Chemoselective Ligation of Sulfinic Acids with Aryl-Nitroso Compounds. Angew Chem Int Ed 51(26):6502–6505
Williams DLH (2003) A chemist’s view of the nitric oxide story. Org Biomol Chem 1(3):441–449
Moran EE, Timerghazin QK, Kwong E, English AM (2011) Kinetics and Mechanism of S-Nitrosothiol Add-Catalyzed Hydrolysis: Sulfur Activation Promotes Facile NO+ Release. J Phys Chem B 115(12):3112–3126
Acknowledgments
Financial support from “Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)” and “French Committee for the Evaluation of Academic and Scientific Cooperation with Brazil (COFECUB)” (grant no. 802-14) is acknowledged. The authors acknowledge financial support for international mobility grant from LabEx MICHEM.
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Ismail, A., d’Orlyé, F., Griveau, S. et al. Capillary electrophoresis with mass spectrometric detection for separation of S-nitrosoglutathione and its decomposition products: a deeper insight into the decomposition pathways. Anal Bioanal Chem 407, 6221–6226 (2015). https://doi.org/10.1007/s00216-015-8786-z
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DOI: https://doi.org/10.1007/s00216-015-8786-z