N-methylated β-carbolines protect PC12 cells from cytotoxic effect of MPP + by attenuation of mitochondrial membrane permeability change

Abstract

Opening of the mitochondrial permeability transition pore has been recognized to be involved in cell death. The present study investigated the effect of β-carbolines (harmaline and harmalol) on the MPP +-induced change in the mitochondrial membrane permeability and cell death in differentiated PC12 cells. β-Carbolines and antioxidants (superoxide dismutase, catalase, ascorbate or rutin) prevented the loss of cell viability in PC12 cells treated with 250 μM MPP +, while the effects of N-acetylcysteine and dithiothreitol were not observed. β-Carbolines reduced the condensation and fragmentation of nuclei caused by MPP + in PC12 cells. β-Carbolines alone did not exhibit a significant cytotoxic effect on PC12 cells. β-Carbolines (50 μM) inhibited the decrease in mitochondrial transmembrane potential, cytochrome c release, activation of caspase-3, formation of reactive oxygen species (ROS) and depletion of GSH caused by MPP + in PC12 cells. β-Carbolines reduced the hydrogen peroxide- or SIN-1-induced cell death in PC12 cells. The results suggest that β-carbolines may attenuate the MPP +-induced viability loss in PC12 cells by inhibition of change in the mitochondrial membrane permeability and by antioxidant effect.