Overexpression of human catalase gene decreases oxidized lipid-induced cytotoxicity in vascular smooth muscle cells

Reactive oxygen metabolites such as hydrogen peroxide (H2O2) and oxidized f atty acids are proinflammatory and are involved in the pathophysiology of v arious diseases including atherosclerosis. The effects of these oxidants co uld be inhibited by the external addition of an antioxidant, suggesting the promotion or propagation of further oxidation. In this study, we describe the stable overexpression of human catalase in smooth muscle cells and the resistance of these cells to cytotoxicity induced not only by the addition of H2O2 but also by the addition of 13-hydroperoxyoctadecadienoic acid (13- HPODE). The results pose an intriguing possibility of the generation of H2O 2 from a peroxidized fatty acid. Accordingly, incubation of cells with both 13-HPODE and 13-hydroxyoctadecadienoic acid resulted in the generation of intracellular H2O2. To explain the observed results by which catalase could overcome the effects of 13-HPODE, we propose that oxidized fatty acids are degraded in the cellular peroxisomes, resulting in the generation of H2O2. In other words, the cellular effects of peroxidized fatty acids could be a ttributed to the generation of H2O2.