Effects of oxidation on functional systems of human serum albumin

Abstract

In order to investigate the effect of oxidative stress on the structure, function and pharmacokinetics of human serum albumin (HSA), oxidized HSAs were prepared by treating with chloramine-T (CT) at various concentrations (0, 1, 10, 50mM). Treatment of HSA with high concentrations of CT (10, 50mM) generated a significant increase in reactive carbonyl content while low concentration of CT (1mM) led to selective oxidation of cysteine (Cys) and methionine (Met). Structural changes were observed in spectroscopic studies of oxidized HSAs treated with 10 and 50mM of CT but not with 1mM of CT. Structural damages resulted from such oxidative stresses altered the binding properties as well as reduced the esterase-like activity of HSA. However, these alterations were little for HSA treated with low concentration of CT. These HSAs were labeled with 125I and were then intravenously administered to rats. The half-lives of the extensively oxidized-HSAs treated with high CT concentrations decreased significantly whereas the half-life for the HSA treated with low CT concentration was comparable to that of the native HSA. In addition, since the half-life of a mutant, C34S, was also comparable to that of the native HSA, selective oxidation of Cys34 hardly leads to conformational and functional changes of HSA. Thus, the present results suggest that the Met residues, together with Cys, play an important role in the antioxidant property of HSA and that oxidation of the Met residues could be the main cause for the structural and functional changes.