Mutual interaction between glycation and oxidation during non-enzymatic protein modification.

Aging pathogenesis involves non-enzymatic modifications of proteins; protein oxidation, glycation and their interactions have aroused a particular interest. Possible interrelations between oxidation and glycation have been evaluated in vitro: bovine serum albumin was oxidized by gamma-irradiation and then exposed to in vitro glycation. Fluorescence modifications induced by radiolytic oxidation and glycation were similar and tended to be additive. Both non-enzymatic processes provoked a loss of free sulfhydryl groups and a strong increment of protein carbonyl content: this supports that glycation can act through oxidative mechanisms. The observed rearrangement of amino groups after irradiation could predispose proteins to glycation attacks. Protein peroxides generated during irradiation appear able to give birth to further protein modifications leading to the generation of carbonyl groups and to interact with monosaccharides, probably stimulating their autoxidation and in turn glycative protein damage. Glycation increases the oxidation-mediated structural damage revealed by SDS-PAGE. Therefore our data support the hypothesis of mutual enhancement between oxidation and glycation of proteins and suggest possible molecular mechanisms of interactions.