Increased formation and degradation of malondialdehyde-modified proteins under conditions of peroxidative stress.

The effect of increased in vivo lipid peroxidation on excretion of the main urinary metabolites of malondialdehyde (MDA) was investigated. peroxidative stress in the form of vitamin E deficiency or the administration of iron nitrilotriacetate or carbon tetrachloride was imposed on rats fed an MDA-free diet. Significant increases were observed in excretion of the lysine-MDA adduct epsilon-propenal lysine, its N-acetyl ester, and free MDA. Under the conditions imposed, the increments in excretion of the lysine adducts reflect increased peroxidative modification of tissue proteins in vivo. These adducts also were found to be the main forms of MDA excreted in human urine. Reacting 14C-bovine serum albumin (BSA) with MDA resulted in its accelerated proteolysis in vitro by soluble enzyme preparations derived from human erythrocytes and rat liver mitochondria. The increments observed were similar to those reported for the hydrolysis of BSA following its exposure to hydroxyl radicals. The results show that lipid peroxidation in vivo results in peroxidative damage to tissue proteins and indicate that such proteins are subject to an accelerated rate of proteolysis.