CHANGES OF ENERGY-METABOLISM INDUCED BY 1-METHYL-4-PHENYLPYRIDINIUM (MPP(-RELATED COMPOUNDS IN RAT PHEOCHROMOCYTOMA PC12 CELLS()))

We examined effects of three structurally related pyridinium compounds , 1-methyl-4-phenylpyridinium (MPP(+)), paraquat, and 1-methyl-4-(4'-n itrophenyl) pyridinium (analog 1), on the energy metabolism in pheochr omocytoma PC12 cells. MPP(+) inhibited the intracellular NADH oxidatio n by the mitochondrial respiratory chain, judging from the decrease of the cytosolic NAD(+)/NADH ratio. Paraquat enhanced the oxidation of N ADH and decreased intracellular ATP more than MPP(+). The inhibition o f 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 increase d a cytosolic ratio of NAD(+)/NADH, and caused only a slight decline o f intracellular ATP. Paraquat was the most cytotoxic of the three comp ounds. Thus, the three structurally related compounds, MPP(+), paraqua t, and analog 1, showed different effects on the mitochondrial respira tory chain and the glycolytic pathway in PC 12 cells, Their properties found in the cells well reflected those obtained by using bovine hear t submitochondrial particles, (C) 1997 Academic Press, Inc.