ER stress and ER stress-mediated apoptosis are involved in manganese-induced neurotoxicity in the rat striatum in vivo

被引：53

作者：

Wang, Ting ^{[1
,2
,3
]}

Li, Xuehui ^{[1
,2
]}

Yang, Dongxu ^{[1
]}

Zhang, Hongtao ^{[1
,2
]}

Zhao, Peng ^{[1
,2
]}

Fu, Juanling ^{[1
]}

Yao, Biyun ^{[1
,2
]}

Zhou, Zongcan ^{[1
]}

机构：

[1] Peking Univ Hlth Sci Ctr, Sch Publ Hlth, Dept Toxicol, Beijing 100191, Peoples R China

[2] Peking Univ Hlth Sci Ctr, Sch Publ Hlth, Beijing Key Lab Toxicol Res & Risk Assessment Foo, Beijing 100191, Peoples R China

[3] Seventh People Hosp Zhengzhou, Zhengzhou Henan 450000, Peoples R China

来源：

NEUROTOXICOLOGY | 2015年 / 48卷

基金：

中国国家自然科学基金;

关键词：

Manganese; Striatum; Endoplasmic reticulum stress; Apoptosis; Neurotoxicity; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; CELL-DEATH; CHLORIDE EXPOSURE; OXIDATIVE STRESS; UPR; ACTIVATION; TRANSPORT; SURVIVAL; DISEASE;

D O I：

10.1016/j.neuro.2015.02.007

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：109 / 119

页数：11