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Role of Aldehyde Dehydrogenase 2 in 1-Methy-4-Phenylpyridinium Ion-Induced Aldehyde Stress and Cytotoxicity in PC12 Cells.
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Neurochem Res 2014 Jul;
Authors: Ai-Hua Chen, Ping Zhang, Wei-Lan Yin, Li Wang, Wei Zou, Xiao-Qing Tang
Aldehyde stress contributes to molecular mechanisms of cell death and the pathogenesis of Parkinson's disease (PD). The neurotoxin 1-Methy-4-Phenylpyridinium Ion (MPP(+)) is commonly used to model PD. Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme detoxifying aldehydes. The aim of this study is to evaluate whether MPP(+)-induced neurotoxicity is involved in aldehyde stress by modulation of ALDH2. Our results demonstrated that treatment of PC12 cells with MPP(+) leads to aldehyde stress by increasing in loads of malondialdehyde and 4-hydroxynonenal, which indicated that MPP(+)-induced aldehyde stress contributes to its cytotoxicity in PC12 cells. We also showed that MPP(+) up-regulates the expression and activity of ALDH2 in PC12 cells and that inhibition of ALDH2 by its specific inhibitor daidzin prevents MPP(+)-induced decrease in cell viability and increases in apoptosis, oxidative stress and aldehyde stress in PC12 cells. These findings suggest that aldehyde stress contributes to MPP(+)-induced toxicity in PC12 cells by upregulation of ALDH2. This study provides a novel insight into the role of ALDH2 in the neurotoxicity of MPP(+).
PMID: 25005621 [PubMed - as supplied by publisher]