Differential effect of catecholamines and MPP⁺ on membrane permeability in brain mitochondria and cell viability in PC12 cells

The present study examined the effect of dopamine, 6-hydroxydopamine (6-OHDA), and MPP⁺ on the membrane permeability transition in brain mitochondria and on viability in PC12 cells. Dopamine and 6-hydroxydopamine induced the swelling and membrane potential change in mitochondria, which was inhibited by addition of antioxidant enzymes, SOD and catalase. In contrast, antioxidant enzymes did not reduce the effect of MPP⁺ on mitochondrial swelling and membrane potential. Catecholamines enhanced the Ca²⁺ uptake and release by mitochondria, and the addition of MPP⁺ induced Ca²⁺ release. Catecholamines induced a thiol oxidation in mitochondria that was decreased by antioxidant enzymes. MPP⁺ showed a little effect on the cytochrome c release from mitochondria and did not induce thiol oxidation. Catecholamines and MPP⁺ induced a cell death, including apoptosis, in PC12 cells that was inhibited by addition of antioxidant enzymes. The result suggests that the oxidation of dopamine and 6-hydroxydopamine could modulate the membrane permeability in brain mitochondria and induce PC12 cell death, which may be ascribed to oxidative stress. MPP⁺ appears to exert a toxic effect on neuronal cells by the action, which is different from catecholamines.