title: Combined effect of dopamine and MPP+ on membrane permeability in mitochondria and cell viability in PC12 cells.
abstract: The present study examined the combined effect of dopamine and 1-methyl-4-phenylpyridinium (MPP(+)) on the membrane permeability in isolated brain mitochondria and on cell viability in PC12 cells. MPP(+) increased effect of dopamine against the swelling, membrane potential, and Ca(2+) transport in isolated mitochondria, which was not inhibited by the addition of antioxidant enzymes (SOD and catalase). Dopamine or MPP(+) caused the decrease in transmembrane potential, increase in reactive oxygen species, depletion of GSH, and cell death in PC12 cells. Antioxidant enzymes reduced each effect of dopamine and MPP(+) against PC12 cells. Co-addition of dopamine and MPP(+) caused the decrease in the transmembrane potential and increase in the formation of reactive oxygen species in PC12 cells, in which they showed an additive effect. Dopamine plus MPP(+)-induced the depletion of GSH and cell death in PC12 cells were not decreased by the addition of antioxidant enzymes, rutin, diethylstilbestrol, and ascorbate. Melanin caused a cell viability loss in PC12 cells. The N-acetylcysteine, N-phenylthiourea, and 5-hydroxyindole decreased the cell death and the formation of dopamine quinone and melanin induced by co-addition of dopamine and MPP(+), whereas deprenyl and chlorgyline did not show an inhibitory effect. The results suggest that co-addition of dopamine and MPP(+) shows an enhancing effect on the change in mitochondrial membrane permeability and cell death, which may be accomplished by toxic quinone and melanin derived from the MPP(+)-stimulated dopamine oxidation.
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, 156-756, Seoul, South Korea. leecs@cau.ac.kr
authors.forename: Chung Soo
authors.initials: CS
authors.lastname: Lee
authors.forename: Eun Hyang
authors.initials: EH
authors.lastname: Song
authors.forename: Se Young
authors.initials: SY
authors.lastname: Park
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Han
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002374:Catalase / Q000378:metabolism / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects* / Q000502:physiology; D007700:Kinetics; D008543:Melanins / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D008933:Mitochondrial Swelling / Q000187:drug effects; D016716:PC12 Cells; D010539:Permeability; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology
chemical_list: D008543:Melanins; C104705:dopamine quinone; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D015655:1-Methyl-4-phenylpyridinium; D002118:Calcium; D004298:Dopamine