The purpose of this study was to quantitatively evaluate the extent of contribution of cysteine-34 ((34) Cys) on the antioxidant effect of human serum albumin (HSA) and to elucidate the physiological implication in hemodialysis (HD) patients. The ratio of oxidized albumin correlated directly with the thiol content in plasma of the HD patients who received intravenous iron. Moreover, the degree of oxidation of (34) Cys in HSA purified from the HD patients' plasma correlated with the thiol content in plasma. The radical scavenging activity of purified HSA was dependent on the degree of (34) Cys oxidation. A recombinant mutant, C34S, was produced to confirm the role of (34) Cys. The activity of C34S was about half of that of wild-type HSA (WT-HSA). Consistent with this observation, the protective effects of C34S were significantly lower than those of WT-HSA in suppressing cytotoxicity and vascular endothelial growth factor production induced by fenton reaction in a human vascular endothelial cell model. These results indicate that the (34) Cys residue of HSA may account for more than 40% of the antioxidant effect of HSA in vivo, and thus may exert a protective effect on vascular endothelium function via an antioxidative mechanism in chronic renal disease.
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