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.