Wang Ting, Li Xuehui, Yang Dongxu, Zhang Hongtao, Zhao Peng, Fu Juanling, Yao Biyun, Zhou Zongcan
Department of Toxicology, School of Public Health, Peking University Health Science Center, Beijing 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, School of Public Health, Peking University Health Science Center, Beijing 100191, PR China; The seventh people hospital of Zhengzhou, Zhengzhou Henan 450000, China.
Department of Toxicology, School of Public Health, Peking University Health Science Center, Beijing 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, School of Public Health, Peking University Health Science Center, Beijing 100191, PR China.
Neurotoxicology. 2015 May;48:109-19. doi: 10.1016/j.neuro.2015.02.007. Epub 2015 Feb 28.
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-6α, 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.
锰（Mn）是一种存在于多种酶中的必需微量元素，然而，过量接触锰会导致锰中毒，其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参与锰诱导的神经毒性。64只SD大鼠随机分为四组，分别腹腔注射生理盐水（NS，作为对照）或氯化锰（分别为7.5、15和30mg/kg体重），持续4周。我们发现氯化锰在纹状体中呈剂量依赖性蓄积。HE染色和TUNEL检测结果表明，氯化锰诱导雄性和雌性大鼠纹状体神经细胞凋亡。超微结构改变显示，氯化锰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，氯化锰增加了大鼠纹状体神经细胞中p-IRE-1、ATF-6α、PERK、GRP78、Sigma-1R、CHOP、Bim、Bax、caspase-12和caspase-3的表达，并降低了Bcl-2的表达。总之，氯化锰可诱导大鼠纹状体神经细胞发生ER应激和ER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。
