Changes of energy metabolism induced by 1-methyl-4-phenylpyridinium (MPP+)-Related compounds in rat pheochromocytoma PC12 cells

Dongchon Kang, Kenichi Miyako, Futoshi Kuribayashi, Eiji Hasegawa, Atsushi Mitsumoto, Tetsuo Nagano, Koichiro Takeshige

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We examined effects of three structurally related pyridinium compounds, 1-methyl-4-phenylpyridinium (MPP+), paraquat, and l-methyl-4-(4'- nitrophenyl) pyridinium (analog 1), on the energy metabolism in pheochromocytoma PC12 cells. MPP+ inhibited the intracellular NADH oxidation by the mitochondrial respiratory chain, judging from the decrease of the cytosolic NAD+/NADH ratio. Paraquat enhanced the oxidation of NADH and decreased intracellular ATP more than MPP+. The inhibition of the mitochondrial respiration by MPP+ was partially compensated by enhanced glycolysis, while paraquat inhibited glycolysis at the level of hexokinase probably due to the intracellular production of oxygen radicals. Analog 1 moderately enhanced glycolysis, moderately increased a cytosolic ratio of NAD+/NADH, and caused only a slight decline of intracellular ATP. Paraquat was the most cytotoxic of the three compounds. Thus, the three structurally related compounds, MPP+, paraquat, and analog 1, showed different effects on the mitochondrial respiratory chain and the glycolytic pathway in PC 12 cells. Their properties found in the cells well reflected those obtained by using bovine heart submitochondrial particles.

元の言語英語
ページ(範囲)75-80
ページ数6
ジャーナルArchives of Biochemistry and Biophysics
337
発行部数1
DOI
出版物ステータス出版済み - 1 1 1997

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

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