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

• Published in: Neuroscience research 2003-07, Vol.46 (3), p.349-358
• Main Authors: Park, Tai Hwan, Kwon, Oh Sang, Park, Se Young, Han, Eun Sook, Lee, Chung Soo
• Format: Article
• Language: English
• Subjects: 1-Methyl-4-phenylpyridinium - pharmacology; Analysis of Variance; Animals; Antioxidants - pharmacology; Apoptosis - drug effects; Carbolines - pharmacology; Caspase 3; Caspases - metabolism; Cell Survival; Cytochrome c Group - metabolism; Dose-Response Relationship, Drug; Drug Interactions; Flow Cytometry; Glutathione - metabolism; GSH depletion; Intracellular Membranes - drug effects; Intracellular Membranes - physiology; Mitochondria - drug effects; Mitochondria - physiology; Mitochondrial membrane permeability; MPP; PC12 Cells; Permeability; Rats; Reactive Oxygen Species - metabolism; Reactive oxygen species formation; β-Carbolines
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/S0168-0102(03)00097-X

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.