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.