| 9241135 |
Hasegawa E, Kang D, Sakamoto K, Mitsumoto A, Nagano T, Minakami S, Takeshige K: A Dual Effect of 1-Methyl-4-phenylpyridinium (MPP+ )-Analogs on the Respiratory Chain of Bovine Heart Mitochondria. Arch Biochem Biophys. 1997 Jan 1;337(1):69-74.
We examined effects of several compounds, structurally related to 1-methyl-4-phenylpyridinium (MPP+ ), on the NADH-dependent respiration of bovine heart submitochondrial particles. 1-Methyl-4-(3'-trimethylammoniophenyl) pyridinium (analog 8) as well as MPP+ completely inhibited O2 consumption, reduction of ubiquinone-10, and reduction of cytochrome b in a dose-dependent manner. The production of superoxide (O- 2 ) induced by MPP+ or analog 8 was to the same extent as that by rotenone, an inhibitor of complex I of the mitochondrial respiratory chain. Rotenone had no additive effect on the maximal production of O- 2 induced by MPP+ or analog 8, suggesting that the production was mediated by the same way as rotenone. 1-Methyl-4-(4'-nitrophenyl) pyridinium (analog 1) induced about 20-fold more production of O- 2 than MPP+ and the production was additively increased by rotenone. Analog 1 only partially inhibited rotenone-sensitive O2 consumption. Paraquat induced the production of O- 2 as much as analog 1. Paraquat, however, did not inhibit rotenone-sensitive O2 consumption or reduction of cytochrome b. These results suggest that MPP+ and its analogs interact with the mitochondrial respiratory chain at two sites, the substrate side of the rotenone-binding site and the rotenone-binding site. The analogs may be reduced to produce O- 2 at the former site and inhibit the respiratory chain at the latter site. |
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