Inhibition of SIN-1-induced change in mitochondrial membrane permeability in PC12 cells by dopamine.
Dopamine (50 or 100 microM) attenuated the nuclear damage and cell death due to 500 microM SIN-1, a donor of superoxide and nitric oxide, in differentiated PC12 cells whereas 200 microM dopamine did not depress cell death. Dopamine at 50-100 microM for a 4-h treatment did not show a significant cytotoxic effect on PC12 cells. Dopamine (100 microM) inhibited the decrease in mitochondrial transmembrane potential, cytochrome c release, activation of caspase-3, formation of reactive oxygen species, and depletion of glutathione (GSH) due to 500 microM SIN-1 in PC12 cells. The reaction of dopamine with peroxynitrite reduced an amount of peroxynitrite. The results suggest that dopamine exhibits a biphasic effect against the cytotoxicity of SIN-1 depending on concentrations. Dopamine at 50-100 microM may attenuate the reactive nitrogen species-induced viability loss in PC12 cells by suppressing the mitochondrial membrane permeability change through inhibition of the formation of reactive species, including peroxynitrite.
Lee
Chung Soo
CS
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea. leecs@cau.ac.kr
Han
Eun Sook
ES
Song
Jin Ho
JH
Kim
Kyung Yong
KY
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000032:analysis; D004298:Dopamine / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D008981:Molsidomine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016716:PC12 Cells; D010539:Permeability; D051381:Rats
C002385:linsidomine; D045304:Cytochromes c; D008981:Molsidomine; D004298:Dopamine