内质网应激及其介导的凋亡在锰致神经毒性中的作用  

Endoplasmic reticulum stress and ERS-mediated apoptosis in manganese-induced neurotoxicity

作　　者：李振宁[1] 米岚[1] 赵鹏[1] 王婷[1] 傅娟玲[1] 姚碧云[1] 周宗灿[1] 

机构地区：[1]北京大学公共卫生学院食品安全毒理学研究与评价北京市重点实验室,北京100191

出　　处：《毒理学杂志》2013年第1期18-22,共5页Journal of Toxicology

基　　金：国家自然科学基金项目(30972502)

摘　　要：目的探讨内质网应激(ERS)及其介导的细胞凋亡在锰引起的神经毒性中的作用。方法以人神经母细胞瘤SH-SY5Y细胞为细胞模型,通过MTT比色法检测MnCl2对细胞存活的影响,流式细胞技术(FCM)检测MnCl2对细胞凋亡的影响,Western blot检测MnCl2作用后,细胞ERS分子伴侣BiP、Sigma-1受体(Sig-1R)、CHOP及凋亡相关蛋白Caspase-4表达的变化。结果 MnCl2可呈时间、剂量依赖性地降低细胞存活率,并诱导SH-SY5Y细胞凋亡;MnCl2上调ERS分子伴侣Bip、Sig-1R、CHOP及Caspase-4的表达。结论 MnCl2可诱导SH-SY5Y细胞发生ERS,早期的ERS对细胞具有保护性效应,持续的ERS通过上调CHOP和Cappase 12的表达介导细胞凋亡,这可能是锰神经毒性机制之一。Objective To explore whether endoplasmic reticulum stress（ERS） and ERS-mediated apoptosis are involved in the mechanisms of manganese-induced neurotoxicity.Methods Using SH-SY5Y cells as the model of dopaminergic neuron,MTT colorimetry test was used to detect the survival state of SH-SY5Y cells in various doses of manganese chloride;apoptosis of SH-SY5Y cells was detected by flow cytometry（FCM）;the expression of endoplasmic reticulum stress chaperone Bip（Grp78）,Sigma-1R,CHOP and Caspase-4 were detected by Western Blot.Results MnCl2 could dose and time-dependently suppress the viability of SH-SY5Y cells and induce SH-SY5Y cells apoptosis.MnCl2 also could promote the expression of ER stress chaperone Bip（Grp78）,Sigma-1R and apoptosis related protein CHOP,Caspase-4.Conclusion MnCl2 could cause endoplasmic reticulum stress in SH-SY5Y cells and induce apoptosis via the pathway of ERS by increasing the expression of CHOP and Caspase4.So,ERS and ERS-mediated apoptosis are involved in the manganese-induced neurotoxicity.

关 键 词：锰 内质网应激 CHOP 凋亡 SH-SY5Y细胞 

分 类 号：R994.6[医药卫生—毒理学]