Changes of energy metabolism induced by 1-methyl-4-phenylpyridinium (MPP+)-related compounds in rat pheochromocytoma PC12 cells.
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| Abstract |
We examined effects of three structurally related pyridinium compounds, 1-methyl-4-phenylpyridinium (MPP+), paraquat, and 1-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.
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| Authors | D Kang, K Miyako, F Kuribayashi, E Hasegawa, A Mitsumoto, T Nagano, K Takeshige |
| Journal | Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 337 Issue 1 Pg. 75-80 (Jan 01 1997) ISSN: 0003-9861 [Print] United States |
| PMID | 8990270 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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