Inhibitory Effect of Rotundarpene on Parkinsonian Neurotoxin 1-Methyl-4-Phenylpyridinium-Induced Apoptotic Cell Death.
- Author:
Sang Woo HAN
1
;
Chung Soo LEE
;
In Ha HWANG
;
Jeong Ho HAN
;
Doo Eung KIM
Author Information
- Publication Type:Original Article
- Keywords: Rotundarpene; 1-methyl-4-phenylpyridinium; PC12 cells; Apoptosis-regulated proteins; Protective effect
- MeSH: 1-Methyl-4-phenylpyridinium; Animals; Apoptosis; Caspase 8; Cell Death*; Cytochromes c; Cytosol; Glutathione; Glycosides; Humans; Ilex; Membrane Potentials; Neuroblastoma; Neurons; Neutral Red; PC12 Cells; Reactive Oxygen Species
- From:Journal of the Korean Neurological Association 2016;34(5):324-332
- CountryRepublic of Korea
- Language:Korean
- Abstract: BACKGROUND: The extract and hemiterpene glycosides of Ilex Rotunda Thunb exert antioxidant and anti-inflammatory effects. The effect of rotundarpene on apoptosis in neuronal cells caused by the 1-methyl-4-phenylpyridinium (MPP⁺) has not been reported previously. METHODS: Using differentiated PC12 cells and human neuroblastoma SH-SY5Y cells, we investigated the effect of rotundarpene on MPP⁺-caused apoptosis in relation to the cell death process. RESULTS: MPP⁺-induced cell death was identified using the MTT and neutral red uptake tests. Apoptosis was induced by eliciting decreases in the cytosolic levels of Bid and Bcl-2 proteins, increases in the cytosolic levels of Bax and p53, disruption of the mitochondrial transmembrane potential, and the release of cytochrome c and the activation of caspase-8, -9, and -3 in differentiated PC12 cells and SH-SY5Y cells. Treatment with rotundarpene reduced the MPP⁺-induced changes in the levels of apoptosis-regulated proteins, formation of reactive oxygen species, depletion and oxidation of glutathione, and cell death in both PC12 and SH-SY5Y cells. CONCLUSIONS: Rotundarpene may reduce MPP⁺-induced apoptosis in neuronal cells by suppressing the activation of the mitochondria-mediated pathway and the caspase-8 and Bid pathways. Rotundarpene appears to act by inhibiting the production of reactive oxygen species and by the depletion and oxidation of glutathione.
