Lipid peroxidation by bovine heart submitochondrial particles stimulated by 1,1′-dimethyl-4,4′-bipyridylium dichloride (paraquat) |
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Authors: | Takeyoshi Sata Koichiro Takeshige Ryoichi Takayanagi Shigeki Minakami |
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Affiliation: | 1. Department of Anesthesiology, Kyushu University School of Medicine, Fukuoka 812, Japan;7. Department of Biochemistry, Kyushu University School of Medicine, Fukuokaa 812, Japan |
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Abstract: | Paraquat enhanced the NADH-dependent lipid peroxidation of bovine heart submitochondrial particles in the presence of ADE-Fe3+ chelate. The enhancement at physiological pH was about 3-fold. The pH optimum of the lipid peroxidation was shifted from pH 6.5 by paraquat. The submitochondrial particles catalyzed the reduction of paraquat when incubated anaerobically with NADH, whereas they did not reduce paraquat with succinate. The reduction was inhibited by phydroxymercuribenzoate or amytal, but it was not inhibited by rotenone, antimycin A or cyanide. The respiratory-chain inhibitors similarly affected the NADH-dependent O2 consumption stimulated by paraquat, indicating that the NADH-dehydrogenase is involved in the reduction of paraquat at a region between the mercurial-sensitive site and the rotenone-sensitive site. The NADH-dependent reduction of ADP-Fe3+ chelate, a key step in lipid peroxidation, was stimulated by paraquat about 5-fold at physiological pH. The stimulation could mainly be ascribed to the direct electron transfer from a paraquat radical to the chelate and partially to the electron transfer from O2? produced by the reoxidation of the paraquat radical. ADP-Fe2+ produced lipid hydroperoxide in liposomes and decomposed cumene hydroperoxide. These reactions, the initiation reaction and the propagation reaction of peroxidation, were stimulated by paraquat. These results suggest that paraquat enhanced lipid peroxidation by stimulating (1) the reduction of ADP-Fe3+ chelate, and (2) the ADP-Fe2+-dependent initiation and propagation reactions of the peroxidation. |
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Keywords: | paraquat 1,1′-dimethyl-4,4′-bipyridylium dichloride MES HEPES 4-(2-hydroxyethyl)-1-piperazine ethane-sulfonic acid |
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