Effect of Alteration of Glutathione Content on Cell Viability in α-Synuclein-Transfected SH-SY5Y Cells  

作　　者：Ken-Ichi Tanaka Kanako Sonoda Masato Asanuma 

机构地区：[1]Physiology and Pharmacology, School of Health and Social Services, Saitama Prefectural University, Koshigaya, Japan [2]Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

出　　处：《Advances in Parkinson's Disease》2017年第3期93-100,共8页帕金森（英文）

摘　　要：It is well known that α-synuclein (αS) plays an important role in the pathogenesis of Parkinson’s disease (PD). Moreover, oxidative stress is also thought to be an important factor in PD due to induction of dopaminergic neuronal cell death by free radicals and enhancement of αS fibrillation by oxidized stress. In the present study, to clarify the role of glutathione (GSH), an intracellular antioxidant, on the molecular mechanism of αS-induced cell injury, we examined the effects of L-buthionine-SR-sulfoximine (BSO), a GSH synthase inhibitor, with or without N-acetyl-L-cysteine (NAC), a source of GSH, on αS-induced cell injury in human neuroblastoma SH-SY5Y cells. Treatment with BSO significantly reduced the cell viability of both empty-vector- and αS-transfected SH-SY5Y cells in a dose-dependent manner (p < 0.01), although the ratio of αS-induced reduction of cell viability in α-syn-transfected cells was much greater than that in empty-vector-transfected cells. Moreover, BSO significantly reduced the intracellular total GSH level in both types of transformant cells. However, NAC significantly prevented BSO-induced reduction of both cell viability and GSH level in the αS-transfected cells. These findings suggest that GSH plays an important role in αS-induced cell injury by reducing cell viability.It is well known that α-synuclein (αS) plays an important role in the pathogenesis of Parkinson’s disease (PD). Moreover, oxidative stress is also thought to be an important factor in PD due to induction of dopaminergic neuronal cell death by free radicals and enhancement of αS fibrillation by oxidized stress. In the present study, to clarify the role of glutathione (GSH), an intracellular antioxidant, on the molecular mechanism of αS-induced cell injury, we examined the effects of L-buthionine-SR-sulfoximine (BSO), a GSH synthase inhibitor, with or without N-acetyl-L-cysteine (NAC), a source of GSH, on αS-induced cell injury in human neuroblastoma SH-SY5Y cells. Treatment with BSO significantly reduced the cell viability of both empty-vector- and αS-transfected SH-SY5Y cells in a dose-dependent manner (p < 0.01), although the ratio of αS-induced reduction of cell viability in α-syn-transfected cells was much greater than that in empty-vector-transfected cells. Moreover, BSO significantly reduced the intracellular total GSH level in both types of transformant cells. However, NAC significantly prevented BSO-induced reduction of both cell viability and GSH level in the αS-transfected cells. These findings suggest that GSH plays an important role in αS-induced cell injury by reducing cell viability.

关 键 词：Α-SYNUCLEIN L-Buthionine-SR-Sulfoximine N-ACETYL-L-CYSTEINE GLUTATHIONE SH-SY5Y Cells Parkinson’s Disease 

分 类 号：R73[医药卫生—肿瘤]