Expressions of inositol requiring enzyme 1α mediated endoplasmic reticulum stress-associated molecules in the hippocampus of rats following status epilepsy
10.3760/cma.j.issn.1006-7876.2013.02.006
- VernacularTitle:大鼠癫痫持续状态后肌醇酶1α介导的内质网应激相关凋亡分子在海马中的表达
- Author:
Gonglu LIU
;
Kaiyan WANG
;
Hui GUO
;
Yongbo ZHAO
- Publication Type:Journal Article
- Keywords:
Status epilepticus;
Endoplasmic reticulum;
Stress;
Endoribonucleases;
Protein-serine-threonine kinases;
JNK mitogen-activated protein kinases;
Caspase 12
- From:
Chinese Journal of Neurology
2013;(2):91-94
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the role of inositol requiring enzyme 1 α (IRE1α) mediated endoplasmic reticulum stress associated apoptotic molecules in hippocampal neuronal injury in rats with status epilepsy following lithium-pilocarpine.Methods All 96 Wistar rats were randomly divided into control group and status epilepsy (SE) group.The SE group was further divided into 5 subgroups (3,6,12,24,48 h) according to different time points.pmmunofluorescence was used to observe the expressions of endoplasmic reticulum stress (ERS) markers glucose-regulating protein 78 kd (GRP78) and phosphoIRE1α (active form of endoplasmic reticulum resident protein IRE1α) at the CA3 area of rats in each group.Then,the expressions of IRElα mediated downstream apoptotie markers phospho-c-JunN-terminalkinase (JNK) and caspase12 were detected.Finally,TUNEL assay was used to observe neuronal apoptosis of hippocampal CA3 area at different time points after SE in rats.Results Immunofluorescence showed that GRP78 and phospho-IRE1α positive neurons were significantly increased in the SE subgroups compared with control group (6.90％ ± 0.96％,4.60％ ± 1.12％,respectively) and 12 h subgroup reached the peak (GRP78:87.45％ ±3.63％,F =356.82,P ＜0.05; phospho-IRE1α:86.90％ ±3.82％,F =300.80,P ＜ 0.05).Immunohistochemistry and Western blot demonstrated that the levels of phospho-JNK and caspase12 in the SE subgroups were significantly higher than that in the control group which reached the peak at 12 h after SE.The changes were in accord with phospho-IRE1α.Simultaneously,hippocampal neuronal apoptosis was detected in each SE subgroup and was most severe at 12 h after SE,which showed similar changes to the expressions of phospho-IRE1α,phospho-JNK and caspase12.Conclusions ERS was induced in rats following SE evidenced by increasing the expression of GRP78.IRE1α may promote hippocampal neuron apoptosis in rats following SE through activating JNK and caspase12.
