Klimek J, Schaap A P, Kimura T
Biochim Biophys Acta. 1983 Jun 16;752(1):127-36. doi: 10.1016/0005-2760(83)90240-0.
We have investigated the effect of paraquat (methyl viologen) on lipid peroxidation in bovine adrenal cortex mitochondria. Incubation of a buffered aerobic mixture of mitochondria in the presence of Fe2+ or NADPH resulted in the formation of lipid peroxides whose accumulation could be followed at 532 nm as malondialdehyde. Fe2+ stimulates lipid peroxidation in normal mitochondria and those in which enzymes have been inactivated with heat. In contrast, NADPH has a stimulatory effect only in normal mitochondria, but not in heat-treated mitochondria. These results indicate that NADPH-dependent lipid peroxidation is an enzymatic process. Paraquat strongly inhibits this enzymatic lipid peroxidation, but has no effect on the non-enzymatic Fe2+-dependent process. The chemiluminescence that accompanies the NADPH-dependent lipid peroxidation is also markedly decreased in the presence of paraquat. Superoxide dismutase, which removes superoxide anion efficiently, does not inhibit malondialdehyde production. The mechanism of the inhibition of the lipid peroxidation by paraquat has been examined. Paraquat has no effect on NADPH-2,6-dichlorophenolindophenol reductase and on NADPH-cytochrome c reductase activities in bovine adrenal cortex mitochondria. However, paraquat strongly inhibits the NADPH-dependent reduction of cytochrome P-450. These results suggest that the inhibitory effect of paraquat on NADPH-dependent lipid peroxidation in adrenal cortex mitochondria is due to a decrease in the level of reduced cytochrome P-450 probably by diverting electrons from cytochrome P-450. Cytochrome c, which can compete with P-450 for available electrons from adrenodoxin, like paraquat had an inhibitory effect on NADPH-dependent lipid peroxidation. Lipid peroxidation was also strongly inhibited by steroid hydroxylase inhibitors, e.g., amphenone B, aminoglutethimide and metyrapone.
我们研究了百草枯（甲基紫精）对牛肾上腺皮质线粒体脂质过氧化的影响。在Fe2+或NADPH存在的情况下，将线粒体的缓冲需氧混合物进行孵育，会导致脂质过氧化物的形成，其积累可在532nm处作为丙二醛进行跟踪。Fe2+刺激正常线粒体以及酶已被热灭活的线粒体中的脂质过氧化。相比之下，NADPH仅对正常线粒体有刺激作用，而对热处理的线粒体没有作用。这些结果表明，NADPH依赖性脂质过氧化是一个酶促过程。百草枯强烈抑制这种酶促脂质过氧化，但对非酶促的Fe2+依赖性过程没有影响。在百草枯存在的情况下，伴随NADPH依赖性脂质过氧化的化学发光也明显降低。能有效清除超氧阴离子的超氧化物歧化酶不会抑制丙二醛的产生。已经研究了百草枯抑制脂质过氧化的机制。百草枯对牛肾上腺皮质线粒体中的NADPH - 2,6 - 二氯酚靛酚还原酶和NADPH - 细胞色素c还原酶活性没有影响。然而，百草枯强烈抑制细胞色素P - 450的NADPH依赖性还原。这些结果表明，百草枯对肾上腺皮质线粒体中NADPH依赖性脂质过氧化的抑制作用可能是由于细胞色素P - 450还原水平的降低，可能是通过从细胞色素P - 450转移电子。细胞色素c可以与P - 450竞争来自肾上腺皮质铁氧化还原蛋白的可用电子，与百草枯一样，对NADPH依赖性脂质过氧化有抑制作用。脂质过氧化也受到类固醇羟化酶抑制剂的强烈抑制，例如氨苯酮B、氨基导眠能和甲吡酮。
