Ischemic preconditioning mediate NMDA receptors through downregulation of c-Jun activation and up-regulation of c-fos in hippocampus CA1

Abstract

OBJECTIVE To explore the role of ERK5 and JNK3 in preconditioning regulation and protein expression with or without CIP and NMDA receptors mediate preconditioning-induced downregulation of c-Jun activation and up-regulation of c-fos in hippocampus CA1. METHODS: MK-801 (10 μM) was administered to rats by unilateral intracerebroventricular infusion (i.c.v.) 20 min prior to preconditioning. The rats were subjected to global cerebral ischemia (GCI) by four-vessel occlusion Rats were subjected to Sham operation (Sham), 8-min global cerebral ischemia + 3d reperfusion (R3d); ischemic preconditioning (P + R3d), ischemic preconditioning + saline + 3d reperfusion (saline), ischemic preconditioning + MK-801 pretreatment + 3d reperfusion (MK-801). Western blotting analysis of the effects of ERK5 and JNK3 in preconditioning regulation and protein expression with or without CIP in hippocampal CA1 regions. RESULTS: global cerebral ischemia significantly increased p-c-Jun as compared to Sham controls. In contrast, preconditioning abolished the global ischemia-induced elevation of p-c-Jun. The effect of preconditioning on p-c-Jun was significantly reversed by pretreatment with the ERK5-AS, while vehicle alone pretreatment had no effect. The changing trend of the C-fos expression was all opposite to that of p-cJun.; Semi-quantitative analysis of the levels of p-c-jun and c-fos levels from the different groups. The influence of ERK5-AS on protein binding activity of p-Bad in cytoplasm and 14-3-3 protein. Immunoprecipitation results showed that Preconditioning significantly increased the protein binding activity of p-Bad and 14-3-3 as compared to 8-min global cerebral ischemia. ERK5-AS apparent reversed the up-regulation. CONCLUSION global cerebral ischemia significantly increased p-c-Jun preconditioning abolished the global ischemia-induced elevation of p-c-Jun. Preconditioning significantly increased the protein binding activity of p-Bad and 14-3-3, ERK5-AS apparent reversed the up-regulation.