The Mechanism of Resveratrol in Preventing Paraquat-induced Cytotoxicity on a Cellular Model of Parkinson's Disease: The Role of Mitochondrial Function.

• Main Authors: Lan-Ya Kang, 康嵐雅
• Other Authors: Chuen-Lin Huang
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/8jq2y8

碩士 === 國防醫學院 === 生理學研究所 === 103 === AAbstract The dopamine neuronal death in the substantia nigra is the unique pathological symptoms of Parkinson's disease (PD), but the reason is still unclear. According to epidemiological studies, higher proportion of PD patients has been exposed to or contacted herbicide. Among the herbicides, paraquat (PQ) is considered to be the main chemical of causing PD in Taiwan. It is well known that PQ-induced neuronal cell death was mediated by inhibiting mitochodrial complex I activity and causing generation of reactive oxygen species. However, PQ how to alter the mitochondrial morphology is still unclear. Resveratrol (Res) has been found to possess strong antioxidant capacity, together with anti-inflammation, anti-cancer, cardiovascular protection and life prolongation. In this study we tried to evaluate the protective effects of Res on the PQ-induced neuronal cell damage, especially in mitochondrial function of SH-SY5Y cells (human neuroblastoma) and rat embryonic E13 dopaminergic neurons. The toxic effects of PQ on SH-SY5Y cells were significantly prevented by cyclosporin A (CsA), a mitochondria permeability transition pore inhibitor, a mitochondria outer membrane permeabilization inhibitor, dibucane (Dibu) and Res. The major way of PQ-induced cell death is apoptosis but not necrosis by Annexin V/ PI immunostaining. Res can markedly attenuate PQ-induced apoptosis. PQ markedly induced mitochondrial morphology from smooth pattern to circle-like by mitotracker staining. Interestingly, only pretreatment of Res can recover PQ-induced circle-like mitochondria. This phenomenon was not seen in pretreatment with CsA and Dibu, even both can effectively suppress the toxicity of PQ. PQ treatment induces increase of cytosolic Bax, Bak, Drp1 and decrease of Bcl2, however, pretreatment with Res can significantly reverse them. The protective effects of Res was disappeared under pretreatment of transcriptional inhibitor (actinomycin D) but not translational inhibitor (cyclohexamide) implied that the protective actions of Res on mitochondrial function and cell survival were mediated the transcriptional gene regulation. In addition, we also demonstrated that pretreatment with Res can obviously shorten the PQ-induced longer time period of beam walk test in 8~10 weeks-old C57BL/ 6N mice. Taken together, our results indicated that pretreatment with Res can protect neuronal cell from PQ-induced damages and it might offer another way for therapeutic and preventing strategies for PQ-induced neuronal cell toxicities.