Lipid peroxidation products mediate damage of superoxide dismutase

Membrane lipid peroxidation processes yield products that may react with superoxide dismutase (SOD), one of the key antioxidant enzymes against oxidative stress, resulting in oxidative modifications. We have investigated this possibility and have found that three types of SOD--CuZnSOD, MnSOD, and FeSOD--exposed to autoxidized linolenate in the presence of Fe3+ caused the loss of dismutase activity, fragmentation of peptides, and an increase in protein oxidation. Lysates from E. coli oxyR strains treated with tert-butyl hydroperoxide, which presumably induces lipid peroxidation, resulted in the activation of SOD. The lipid peroxidation-mediated damage to SOD may result in the perturbation of cellular antioxidant defense mechanisms and subsequently lead to a pro-oxidant condition.