Lead inhibits microglial cell migration via suppression of store-operated calcium entry

被引:2
作者
Tang, Wei [1 ,2 ,3 ]
Peng, Jiawen [1 ,2 ,3 ]
Chen, Lixuan [1 ,2 ,3 ]
Yu, Changhui [1 ,2 ,3 ]
Wang, Yuhao [1 ,2 ,3 ]
Zou, Fei [1 ,2 ,3 ]
Zheng, Gang [1 ,2 ,3 ]
Meng, Xiaojing [1 ,2 ,3 ,4 ]
机构
[1] Southern Med Univ, Sch Publ Hlth, Dept Occupat Hlth & Occupat Med, Guangdong Prov Key Lab Trop Dis Res, Guangzhou, Guangdong, Peoples R China
[2] Fourth Mil Med Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth, Xian 710032, Peoples R China
[3] Fourth Mil Med Univ, Sch Publ Hlth, Minist Educ Key Lab Hazard Assessment & Control Sp, Xian 710032, Peoples R China
[4] Southern Med Univ, Sch Publ Hlth, Dept Occupat Hlth & Occupat Med, 1838 Guangzhou Dadaobei, Guangzhou, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
Lead; Microglia; Neuroinflammation; Migration; Store-operated calcium entry; EXPOSURE; STIM1; PB2+; LIPOPOLYSACCHARIDE; CYTOTOXICITY; PHAGOCYTOSIS; TOXICITY; ORAI1;
D O I
10.1016/j.toxlet.2024.01.011
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Lead (Pb) is a non-biodegradable environmental pollutant that can lead to neurotoxicity by inducing neuroinflammation. Microglial activation plays a key role in neuroinflammation, and microglial migration is one of its main features. However, whether Pb affects microglial migration has not yet been elucidated. Herein, the effect of Pb on microglial migration was investigated using BV-2 microglial cells and primary microglial cells. The results showed that cell activation markers (TNF-alpha and CD206) in BV-2 cells were increased after Pb treatment. The migration ability of microglia was inhibited by Pb. Both store-operated calcium entry (SOCE) and the Ca2+ release-activated Ca2+ (CRAC) current were downregulated by microglia treatment with Pb in a dose-dependent manner. However, there was no statistical difference in the protein levels of stromal interaction molecule (STIM) 1, STIM2, or Ca2+ release-activated Ca2+ channel protein (Orai) 1 in microglia. The external Ca2+ influx and cell migration ability were restored to a certain extent after overexpression of either STIM1 or its CRAC activation domain in microglia. These results indicated that Pb inhibits microglial migration by downregulation of SOCE and impairment of the function of STIM1.
引用
收藏
页码:69 / 77
页数:9
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