Oxidative stress involvement in manganese-induced alpha-synuclein oligomerization in organotypic brain slice cultures
Oxidative stress involvement in manganese-induced alpha-synuclein oligomerization in organotypic brain slice cultures
复制标题
氧化应激参与器官型脑切片培养物中锰诱导的α-突触核蛋白寡聚化
DOI：
10.1016/j.tox.2013.01.006
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发表时间：
2013-03-08
期刊：
影响因子：
4.5
通讯作者：
Xu, Zhao-Fa
中科院分区：
文献类型：
--
作者：
Xu, Bin;Wu, Sheng-Wen;Xu, Zhao-Fa
已知锰（Mn）过量可诱导神经元损伤。然而，很少有人知道的作用，活性氧（ROS）发挥蛋白质聚集造成锰暴露。目前的研究调查氧化应激是否参与锰诱导的α-突触核蛋白寡聚化的器官型脑切片。应用锰（0-400 μ M）24小时后，有一个剂量依赖性的增加，碘化丙啶阳性（PI+）细胞核的平均百分比在切片和乳酸脱氢酶（LDH）在培养基中的水平。此外，锰处理导致神经细胞凋亡，ROS水平的剂量依赖性增加，超氧化物歧化酶（SOD）活性下降。锰还引起细胞脂质和蛋白质的氧化损伤。同时，锰暴露导致α-突触核蛋白mRNA和蛋白表达显著增加。α-突触核蛋白寡聚化发生在锰处理的切片，特别是在膜结合的形式。这表明α-synuclein寡聚体更容易结合细胞膜，导致膜损伤。Mn诱导的神经细胞损伤和α-突触核蛋白寡聚化也部分减轻预处理与GSH和加重H2 O2预处理。研究结果表明，锰可能发挥其神经毒性作用的氧化应激介导的α-突触核蛋白寡聚化的器官型脑片。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Overexposure to manganese (Mn) has been known to induce neuronal damage. However, little is known of the role that reactive oxygen species (ROS) play in protein aggregation resulting from Mn exposure. The current study investigated whether oxidative stress is involved in manganese-induced alpha-synuclein oligomerization in organotypic brain slices. After application of Mn (0-400 mu M) for 24 h, there was a dose-dependent increase in average percentage of propidium iodide positive (PI+) nuclei in slices and levels of lactate dehydrogenase (LDH) in the culture medium. Moreover, the treatment with Mn resulted in a dose-dependent increase in neurocyte apoptosis, ROS level, and decrease in superoxide dismutase (SOD) activity. Mn also caused oxidative damage in cell lipid and protein. At the same time, the exposure of Mn leaded to significantly increase in the expression of alpha-synuclein mRNA and protein. Alpha-synuclein oligomerization occurred in Mn-treated slices, especially on membrane-bound form. It indicated that alpha-synuclein oligomers were more likely to combination cell membranes and resulting in membrane damage. Mn-induced neurocyte damage and alpha-synuclein oligomerization were also partially alleviated by the pretreatment with GSH and aggravated by H2O2 pretreatment. The findings revealed Mn might exert its neurotoxic effects by oxidative stress-mediated alpha-synuclein oligomerization in organotypic brain slices. (C) 2013 Elsevier Ireland Ltd. All rights reserved.