Overexpression of human catalase gene decreases oxidized lipid-induced cytotoxicity in vascular smooth muscle cells.
Reactive oxygen metabolites such as hydrogen peroxide (H(2)O(2)) and oxidized fatty acids are proinflammatory and are involved in the pathophysiology of various diseases including atherosclerosis. The effects of these oxidants could 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 H(2)O(2) but also by the addition of 13-hydroperoxyoctadecadienoic acid (13-HPODE). The results pose an intriguing possibility of the generation of H(2)O(2) from a peroxidized fatty acid. Accordingly, incubation of cells with both 13-HPODE and 13-hydroxyoctadecadienoic acid resulted in the generation of intracellular H(2)O(2). 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 H(2)O(2). In other words, the cellular effects of peroxidized fatty acids could be attributed to the generation of H(2)O(2).
Santanam
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Department of Gynecology and Obstetrics, Emory University, Atlanta, GA, USA.
Aug
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Zhou
M
M
Keshava
C
C
Parthasarathy
S
S
D000818:Animals; D002374:Catalase / Q000235:genetics*; D018076:DNA, Complementary / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D008041:Linoleic Acids; D008054:Lipid Peroxides; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D010084:Oxidation-Reduction; D011817:Rabbits / Q000276:immunology; D014162:Transfection
D018076:DNA, Complementary; D008041:Linoleic Acids; D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; C038649:13-hydroperoxy-9,11-octadecadienoic acid; D006861:Hydrogen Peroxide; D002374:Catalase