ER stress and ER stress-mediated apoptosis are involved in manganese-induced neurotoxicity in the rat striatum in vivo
ER stress and ER stress-mediated apoptosis are involved in manganese-induced neurotoxicity in the rat striatum in vivo
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DOI：
10.1016/j.neuro.2015.02.007
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发表时间：
2015-05-01
期刊：
影响因子：
3.4
通讯作者：
Zhou, Zongcan
中科院分区：
文献类型：
--
作者：
Wang, Ting;Li, Xuehui;Zhou, Zongcan
锰 (Mn) 是许多酶中的必需微量元素，然而，过量接触锰会导致锰中毒，类似于帕金森氏运动障碍。锰中毒的机制尚不清楚。本体内研究旨在确定内质网应激（ER 应激）和 ER 应激介导的细胞凋亡是否与锰诱导的神经毒性有关。 64只SD大鼠随机分为4组，腹腔注射生理盐水（NS，作为对照）或MnCl2（分别为7.5、15和30 mg/kg体重），连续4周。我们发现 MnCl2 在纹状体中呈剂量依赖性积累。 HE染色和TUNEL检测结果表明，MnCl2可诱导雄性和雌性大鼠纹状体神经细胞凋亡。超微结构的改变表明，MnCl2导致大鼠纹状体神经细胞染色质浓缩、线粒体和内质网肿胀。此外，MnCl2 增加大鼠纹状体神经细胞中 p-IRE-1、ATF-6 α、PERK、GRP78、Sigma-1R、CHOP、Bim、Bax、caspase-12 和 caspase-3 的表达，并降低 Bcl-2 的表达。总之，MnCl2可诱导大鼠纹状体神经细胞内质网应激及内质网应激介导的细胞凋亡，这可能是锰诱导神经毒性的重要机制之一。 (C) 2015 Elsevier Inc. 保留所有权利。
Manganese (Mn) is an essential trace element found in many enzymes, however, excessive Mn-exposure can result in manganism which is similar to Parkinson's movement disorder. The mechanisms of manganism are not well-known. The present in vivo study was carried out to determine whether endoplasmic reticulum stress (ER stress) and ER stress-mediated apoptosis are involved in manganese-induced neurotoxicity. Sixty-four SD rats were randomly divided into four groups and were administered intraperitoneally with normal saline (NS, as control) or MnCl2 (7.5, 15 and 30 mg/kg body weight, respectively) for 4 weeks. We found that MnCl2 dose-dependently accumulate in striatal. HE staining and TUNEL assay results indicated that MnCl2 induced striatal neurocytes apoptosis in both male and female rats. The alterations of ultrastructures showed that MnCl2 resulted in chromatin condensation, mitochondria and ER tumefaction in rat striatal neurocytes. Furthermore, MnCl2 increased the expressions of p-IRE-1, ATF-6 alpha, PERK, GRP78, Sigma-1R, CHOP, Bim, Bax, caspase-12 and caspase-3, and decreased the expression of Bcl-2 in rat striatal neurocytes. In conclusion, MnCl2 could induce ER stress and ER stress-mediated apoptosis in rat striatal neurocytes, which might be one of the important mechanisms of Mn-induced neurotoxicity. (C) 2015 Elsevier Inc. All rights reserved.