MUTUAL INTERACTION BETWEEN GLYCATION AND OXIDATION DURING NONENZYMATIC PROTEIN MODIFICATION

Aging pathogenesis involves non-enzymatic modifications of proteins; p rotein oxidation, glycation and their interactions have aroused a part icular interest. Possible interrelations between oxidation and glycati on 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 simi lar and tended to be additive. Both non-enzymatic processes provoked a loss of free sulfhydryl groups and a strong increment of protein carb onyl content: this supports that glycation can act through oxidative m echanisms. The observed rearrangement of amino groups after irradiatio n could predispose proteins to glycation attacks. Protein peroxides ge nerated during irradiation appear able to give birth to further protei n modifications leading to the generation of carbonyl groups and to in teract with monosaccharides, probably stimulating their autoxidation a nd in turn glycative protein damage. Glycation increases the oxidation -mediated structural damage revealed by SDS-PAGE. Therefore our data s upport the hypothesis of mutual enhancement between oxidation and glyc ation of proteins and suggest possible molecular mechanisms of interac tions. (C) 1997 Elsevier Science B.V.