Mn-Induced Neurocytes Injury and Autophagy Dysfunction in Alpha-Synuclein Wild-Type and Knock-Out Mice: Highlighting the Role of Alpha-Synuclein

被引:32
|
作者
Yan, Dong-Ying [1 ]
Liu, Chang [1 ]
Tan, Xuan [1 ]
Ma, Zhuo [1 ]
Wang, Can [1 ]
Deng, Yu [1 ]
Liu, Wei [1 ]
Xu, Zhao-Fa [1 ]
Xu, Bin [1 ]
机构
[1] China Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang North New Area, 77 Puhe Rd, Shenyang 110122, Liaoning, Peoples R China
基金
中国国家自然科学基金;
关键词
Manganese; Alpha-synuclein oligomerization; Autophagy; Apoptosis; Neurotoxicity; CHAPERONE-MEDIATED AUTOPHAGY; PARKINSONS-DISEASE; MANGANESE; STRESS; MACROAUTOPHAGY; DEGRADATION; CROSSTALK; MODEL;
D O I
10.1007/s12640-019-00016-y
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Overexposure to manganese (Mn) is an important environmental risk factor for Parkinsonian-like symptoms referred to as manganism. Alpha-synuclein (-Syn) oligomerization is a major cause in Mn-induced neurotoxicity. Autophagy, as an adjust response to control intracellular protein homeostasis, is involved in the degradation of -Syn monomers or oligomers. Furthermore, autophagy dysregulation is also related to development of neurodegenerative disorders. Hence, we speculated that there was an interaction effect between -Syn oligomerization and autophagy upon Mn exposure. In this study, we applied -Syn gene knockout mice (-Syn(-/-)) and wild-type mice (-Syn(+/+)) treated with three different concentrations of MnCl2 (50, 100, and 200mol/kg) to elucidate the physiological role of -Syn in Mn-induced autophagy dysregulation and neurocytes injury. We found that activation of chaperone-mediated autophagy (CMA) pathway by Mn was independent of -Syn. Additionally, -Syn could ameliorate excessive autophagy induced by high dose Mn (200mol/kg). Next, we used 5mg/kg Rapamycin (Rap) or 3-methyladenine (3-MA) to regulate autophagy. The study revealed that autophagy is involved in Mn-induced -Syn oligomerization and neurocytes injury. Taken together, these findings indicated that -Syn oligomerization might be the major responsible for the Mn-induced autophagy dysregulation and neurocytes injury.
引用
收藏
页码:66 / 80
页数:15
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