Mechanism of CCAAT/enhancer-binding protein-homologous protein mediated endoplasmic reticulum stress involving in the epileptic brain damage / 中华实用儿科临床杂志

ABSTRACT

Objective To explore the neuronal apoptosis,endoplasmic reticulum stress(ERS)-related factors glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein-homologous protein (CHOP) expressions in hippocampus and possible mechanism of brain protection by 2-deoxy-D-glucose(2-DG) on their expressions in epileptic brain damage rats induced by pentetrazole.Methods Rats aged 21 d (n =120) were randomly divided into 3 groupscontrol group,status epilepticus (SE) group and SE + DG group,with 40 rats in each group.On a SE rat model,the neuronal apoptosis in the hippocampus was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling method.And the expression of GRP78 and CHOP were detected by Western blot and Real-time PCR.Results Apoptotic cells in the hippocampus were increased remarkably at 12 h,24 h,and 48 h after the seizures,as compared with those of control rats.In SE group,chromatin condensation and breakdown of the nucleus in neurons in hippocampus were also easily observed by Hoechst staining.Meanwhile,the ERS was induced by SE,as witness by up-regulating GRP78 expression at both protein and mRNA level.The expression of GRP78 protein in the hippocampus was elevated at 3 h,6 h and 12 h,with the maximum elevation noted at 6 h after SE.The GRP78 transcript expression was increased at 3 h,6 h,and 12 h after SE.DG treatment enhanced the changes of GRP78 protein and transcript at 3 h,and abrogated the increase of GRP78 at 6 h and 12 h,as compared with those in SE group.CHOP activation occurred at 12 h,24 h and 48 h in SE group.And the CHOP-mRNA expression was the same as the CHOP protein expression.The expression of CHOP protein and mRNA was decreased at 12 h,24 h,and 48 h after using DG.Conclusion The endoplasmic reticulum stress response mediated by CHOP seems to be involved in the neuronal apoptosis caused by status epilepticus.