Tsikas D, Sandmann J, Luessen P, Savva A, Rossa S, Stichtenoth D O, Frölich J C
Institute of Clinical Pharmacology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625, Hannover, Germany.
Biochim Biophys Acta. 2001 Apr 7;1546(2):422-34. doi: 10.1016/s0167-4838(01)00166-2.
S-Nitrosoalbumin (SNOALB) is the most abundant physiological circulating nitric oxide (NO) carrier regulating NO-dependent biological actions in humans. The mechanisms of its formation and biological actions are still incompletely understood. Nitrosation by authentic NO and S-transnitrosylation of the single sulfhydryl group located at Cys-34 of human albumin by the physiological S-nitroso compounds S-nitrosocysteine (SNOC) and S-nitrosoglutathione (GSNO) are two possible mechanisms. On a quantitative basis, we investigated by gas chromatography-mass spectrometry the contribution of these two mechanisms to SNOALB formation in human plasma and blood in vitro. GSNO and SNOC (0-100 microM) rapidly and efficiently (recovery=35%) S-transnitrosylated albumin to form SNOALB. NO (100 microM) S-nitrosated albumin to SNOALB at a considerably lower extent (recovery=5%). The putative NO-donating drugs glyceryl trinitrate and sodium nitroprusside (each 100 microM) failed completely in S-nitrosating albumin. Bubbling NO into human plasma and blood resulted in formation of SNOALB that inhibited ADP-induced platelet aggregation. Infusion of GS(15)NO in the rat resulted in formation of S(15)NOALB, [(15)N]nitrate and [(15)N]nitrite. Our results suggest that S-transnitrosylation of albumin by SNOC and GSNO could be a more favored mechanism for the formation of SNOALB in the circulation in vivo than S-nitrosation of albumin by NO itself.
S-亚硝基白蛋白（SNOALB）是人体中调节一氧化氮（NO）依赖性生物学作用的最丰富的生理性循环NO载体。其形成机制和生物学作用仍未完全明确。由真实的NO进行亚硝化以及生理S-亚硝基化合物S-亚硝基半胱氨酸（SNOC）和S-亚硝基谷胱甘肽（GSNO）对人白蛋白位于Cys-34的单个巯基进行S-转亚硝化是两种可能的机制。在定量基础上，我们通过气相色谱-质谱法研究了这两种机制对人血浆和体外血液中SNOALB形成的贡献。GSNO和SNOC（0 - 100微摩尔）能快速有效地（回收率 = 35%）将白蛋白进行S-转亚硝化以形成SNOALB。NO（100微摩尔）将白蛋白亚硝化生成SNOALB的程度要低得多（回收率 = 5%）。假定的NO供体药物硝酸甘油和硝普钠（各100微摩尔）完全无法将白蛋白亚硝化。向人血浆和血液中鼓入NO会导致形成抑制ADP诱导的血小板聚集的SNOALB。在大鼠中输注GS(15)NO会导致形成S(15)NOALB、[(15)N]硝酸盐和[(15)N]亚硝酸盐。我们的结果表明，与NO自身对白蛋白的亚硝化相比，SNOC和GSNO对白蛋白的S-转亚硝化可能是体内循环中形成SNOALB更有利的机制。
