TY - JOUR
T1 - A dual effect of 1-methyl-4-phenylpyridinium (MPP+)-Analogs on the respiratory chain of bovine heart mitochondria
AU - Hasegawa, Eiji
AU - Kang, Dongchon
AU - Sakamoto, Kei
AU - Mitsumoto, Atsushi
AU - Nagano, Tetsuo
AU - Minakami, Shigeki
AU - Takeshige, Koichiro
N1 - Funding Information:
1This work was supported by a research grant from the Ministry of Education, Science, and Culture of Japan. 2 Present address; Department of Neurology, University of Occupational and Environmental Health, Kitakyushu 807, Japan. 3To whom correspondence should be addressed. Fax: 81(Japan)-92-632-2373.
PY - 1997/1/1
Y1 - 1997/1/1
N2 - 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 (O2) 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 O2 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 O2 than MPP+ and the production was additively increased by rotenone. Analog 1 only partially inhibited rotenonesensitive O2 consumption. Paraquat induced the production of O2 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 rotenonebinding site and the rotenone-binding site. The analogs may be reduced to produce O2 at the former site and inhibit the respiratory chain at the latter site.
AB - 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 (O2) 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 O2 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 O2 than MPP+ and the production was additively increased by rotenone. Analog 1 only partially inhibited rotenonesensitive O2 consumption. Paraquat induced the production of O2 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 rotenonebinding site and the rotenone-binding site. The analogs may be reduced to produce O2 at the former site and inhibit the respiratory chain at the latter site.
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U2 - 10.1006/abbi.1996.9726
DO - 10.1006/abbi.1996.9726
M3 - Article
C2 - 9395404
AN - SCOPUS:0030990293
SN - 0003-9861
VL - 337
SP - 69
EP - 74
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 1
ER -