1-Methyl-4-phenylpyridinium (MPP+) inhibits mitochondrial oxygen consumption mediated by succinate as well as malate in rat pheochromocytoma PC12 cells.
When rat pheochromocytoma PC12 cells are cultured with 1 mM 1-methyl-4-phenylpyridinium (MPP+), the number of viable cells decreases to one third in 4 days while the number increases ten-fold without MPP+. Oxygen consumption by mitochondria in the presence of malate is inhibited about 80% by the treatment of the cells with MPP+ for 4 days. Unexpectedly, succinate-dependent oxygen consumption is also inhibited to essentially the same extent as malate-dependent one. These results suggest that the impairment of the respiration mediated by succinate as well as malate is important as a mechanism of MPP(+)-induced cell death.
Hasegawa
E
E
Department of Biochemistry, Kyushu University School of Medicine, Fukuoka, Japan.
Asagami
H
H
Kang
D
D
Minakami
S
S
Takeshige
K
K
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000310:Adrenal Gland Neoplasms; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008293:Malates / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D016716:PC12 Cells; D010673:Pheochromocytoma; D051381:Rats; D013386:Succinates / Q000378:metabolism*; D013997:Time Factors
D008293:Malates; D013386:Succinates; D015655:1-Methyl-4-phenylpyridinium