MKP1 reduces neuroinflammation via inhibiting endoplasmic reticulum stress and mitochondrial dysfunction

被引:13
作者
Huang, Dezhi [1 ]
Jiang, Yugang [1 ]
机构
[1] Cent S Univ, Xiangya Hosp 2, Dept Neurosurg, 139 Renmin Rd, Changsha 410000, Hunan, Peoples R China
关键词
BV-2; cells; ER stress; LPS; mitochondrial damage; MKP1; neuroinflammation; OXIDATIVE STRESS; DEFICIENCY; INJURY; CELLS;
D O I
10.1002/jcp.29308
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
MAP kinase phosphatase 1 (MKP1) has been identified as an antiapoptotic protein via sustaining mitochondrial function. However, the role of MKP1 in neuroinflammation has not been fully understood. The aim of this study is to figure out the influence of MKP1 in lipopolysaccharide (LPS)-treated microglia BV-2 cells and investigate whether MKP1 reduces BV-2 cell death via modulating endoplasmic reticulum (ER) stress and mitochondrial dysfunction. The results of this study demonstrated that MKP1 was rapidly downregulated after exposure to LPS. However, the transfection of MKP1 adenovirus could reverse cell viability and attenuate LPS-mediated BV-2 cell apoptosis. Mechanistically, MKP1 overexpression alleviated ER stress and corrected LPS-induced calcium overloading. Besides, MKP1 adenovirus transfection also reversed mitochondrial bioenergetics, maintained mitochondrial membrane potential, and blocked mitochondria-initiated apoptosis signals. Furthermore, we found that MKP1 overexpression is associated with inactivation of mitogen-activated protein kinase-c-Jun N-terminal kinase (MAPK-JNK) pathway. Interestingly, the activation of MAPK-JNK pathway could abolish the protective effects of MKP1 on BV-2 cells survival and mitochondrial function in the presence of LPS. Altogether, our results identified MKP1 as a primary defender of neuroinflammation via modulating ER stress and mitochondrial function in a manner dependent on MAPK-JNK pathway. These findings may open a new window for the treatment of neuroinflammation in the clinical setting.
引用
收藏
页码:4316 / 4325
页数:10
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