Comparison of the Protective Effect of Indole beta-carbolines and R-(-)-deprenyl Against Nitrogen Species-Induced Cell Death in Experimental Culture Model of Parkinson's Disease.
- Author:
Young Su HAN
1
;
Jung Mee KIM
;
Jeong Seon CHO
;
Chung Soo LEE
;
Doo Eung KIM
Author Information
- Publication Type:Original Article
- Keywords: Indole beta-carbolines; Nitrogen species; Mitochondrial membrane permeability; Cell death; Differentiated PC12 cells
- MeSH: Animals; Antioxidants; Carbolines*; Caspase 3; Caspases; Cell Death*; Cell Survival; Cytochromes c; Dithiothreitol; Free Radicals; Melatonin; Membrane Potentials; Membranes; Mitochondria; Mitochondrial Membranes; Neurons; Neurotoxins; Nitrogen*; Parkinson Disease*; PC12 Cells; Permeability; Reactive Nitrogen Species; Reactive Oxygen Species
- From:Journal of Clinical Neurology 2005;1(1):81-91
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND: The membrane permeability transition of mitochondria has been suggested to be involved in toxic and oxidative forms of cell injury. Mitochondrial dysfunction is considered to play a critical role in neurodegeneration in Parkinson's disease. Despite the suggestion that indole beta-carbolines may be neurotoxic, these compounds provide a protective effect against cytotoxicity of other neurotoxins. In addition, the effect of indole beta-carbolines on change in the mitochondrial membrane permeability due to reactive nitrogen species (RNS), which may lead to cell death, has not been clarified. METHODS: Differentiated PC12 cells were used as the experimental culture model for the investigation of neuronal cell injury, which occurs in Parkinson's disease. The effect of indole beta-carbolines (harmalol and harmine) on differentiated PC12 cells against toxicity of S-nitroso-N-acetyl-DL-penicillamine (SNAP) was determined by measuring the effect on the change in transmembrane potential, cytochrome c release, formation of ROS, GSH contents, caspase-3 activity and cell viability, and was compared to that of R-(-)-deprenyl. RESULTS: Specific inhibitors of caspases (z-LEHD.fmk, z-DQMD.fmk) and antioxidants (N-acetylcysteine, dithiothreitol, melatonin, carboxy-PTIO and uric acid) depressed cell death in PC12 cells due to SNAP. beta-Carbolines and R-(-)-deprenyl attenuated the SNAP-induced cell death and GSH depletion concentration dependently with a maximal inhibitory effect at 25-50 microM. The compounds inhibited the nuclear damage, decrease in mitochondrial transmembrane potential, cytochrome c release and formation of reactive oxygen species caused by SNAP in PC12 cells. beta-Carbolines and R-(-)-deprenyl attenuated the H2O2-induced cell death and depletion of GSH. CONCLUSIONS: The results suggest that indole beta-carbolines attenuate the SNAP-induced viability loss in PC12 cells by inhibition of change in the mitochondrial membrane permeability, which may be caused by free radicals. Indole beta-carbolines appear to exert a protective effect against the nitrogen species-mediated neuronal cell injury in Parkinson's disease comparable to R-(-)-deprenyl.
