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. P eroxidative stress in the form of vitamin E deficiency or the administ ration of iron nitrilotriacetate or carbon tetrachloride was imposed o n rats fed an MDA-free diet. Significant increases were observed in ex cretion 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 modific ation of tissue proteins in vivo. These adducts also were found to be the main forms of MDA excreted in human urine. Reacting C-14-bovine se rum albumin (BSA) with MDA resulted in its accelerated proteolysis in vitro by soluble enzyme preparations derived from human erythrocytes a nd rat liver mitochondria. The increments observed were similar to tho se reported for the hydrolysis of BSA following its exposure to hydrox yl radicals. The results show that lipid peroxidation in vivo results in peroxidative damage to tissue proteins and indicate that such prote ins are subject to an accelerated rate of proteolysis.