The changes of mitochondrial unfolded protein response in epileptic hippocampal neurons and the effect of mitochondria-targeted antioxidant Mito-TEMPO
10.19845/j.cnki.zfysjjbzz.2022.0106
- VernacularTitle:线粒体未折叠蛋白反应在癫痫海马神经中的变化及线粒体特异性抗氧化剂对其影响
- Author:
Nanchang XIE
1
;
Xiaomeng YU
1
;
Xiaoyi WANG
1
Author Information
1. Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
- Publication Type:Journal Article
- Keywords:
Epilepsy;
Oxidative stress;
Mitochondria-targeted antioxidant;
Mitochondrial unfolded protein response
- From:
Journal of Apoplexy and Nervous Diseases
2022;39(5):414-418
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the changes of mitochondrial unfolded protein response (mtUPR) in hippocampus of lithium-pilocarpine induced seizures and the effect of mitochondria-targeted antioxidant. Methods Lithium chloride and pilocarpine were used to elicit status epilepticus in rats, and the rats were further treated with mitochondria-targeted antioxidant Mito-TEMPO. Adult male Wistar rats were randomly divided into control group, PILO group, Mito-TEMPO group and PILO +Mito-TEMPO group. Nissl staining was used to observe the damage of hippocampal neurons, electron transmission microscopy was used to observe the ultrastructure of mitochondria, ROS production of mitochondria was detected by reactive oxygen species fluorescent probe (DCFDA), and mitochondrial membrane potential was detected by Rhoda.mine123 staining. The expressions of mitochondrial heat shock protein HSP60, protease LONP1 and mitochondrial protease CLpP were detected by Western blot. Results (1) Compared with CON group, the ultrastructure of hippocampal neuronal mitochondria in PILO group was seriously damaged, mitochondrial ROS production was increased, and mitochondrial membrane potential was decreased. (2) Compared with the CON group, the expressions of HSP60 , Lonp1 and CLpP in the PILO group were increased. (3) Compared with the PILO group, the damage of mitochondrial ultrastructure was alleviated in the PILO+Mito-TEMPO group, the production of mitochondrial ROS was significantly reduced, and the mitochondrial membrane potential was increased. (4) Compared with the PILO group, the expressions of HSP60, LONP1 and CLpP in the hippocampal neurons of the PILO+Mito-TEMPO group were decreased. Conclusion The mtUPR is significantly activated in hippocampal neurons in epilepsy, and Mito-TEMPO may play a protective role in hippocampal mitochondrial injury in epilepsy regulating mtUPR.
- Full text:202407242214093155The changes of mitochondrial unfolded protein response in epileptic hippocampal neurons and the effect of mitochondria-targeted antioxidant Mito-TEMPO.pdf