Characterization of oxidation end product of plasma albumin ‘in vivo’

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• 作者：Luca Musante ; Maurizio Bruschi ; Giovanni Candiano ; Andrea Petretto ; Nazzareno Dimasi ; Piero Del Boccio ; Andrea Urbani ; Giovanni Rialdi and Gian Marco Ghiggeri
• 关键词：Free radicals ; Plasma albumin ; Nephrotic syndrome ; Antioxidant functions
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2006
• 出版时间：20 October 2006
• 年：2006
• 卷：349
• 期：2
• 页码：668-673
• 全文大小：199 K

文摘

Anti-oxidants are paradoxically much lower in plasma than inside cells even blood is comparably exposed to the oxidative stress. ‘In vitro’ models suggest a critical role of albumin as substitutive anti-oxidant in plasma but no proof for this role is available ‘in vivo.’ Herein, we demonstrate by LC/MS/MS that plasma albumin undergoes massive oxidation in primary nephrotic syndrome, involving stable sulphonation of the free SH of Cys 34 with +48 Da increase in exact mass of the protein (ESI-MS) and formation of a fast moving isoform in the pH range between 5 and 7. Physical–chemical experiments with DSC and fluorescence spectra indicate a thermal stabilization of the structure upon oxidation. This is the first demonstration of massive oxidation of albumin ‘in vivo’ that reflects a functional role of the protein. Free radicals should be implicated in the pathogenesis of proteinuria in human FSGS.