Regulation of ERK signaling pathway in HIF-1α expression in the hippocampus of epileptic rats

Abstract

Objective To explore whether extracellular signal-reg-ulated kinase (ERK) signaling pathway is involved in the hypoxia-inducible factor-1α (HIF-1α) expression in the hippocampus of epileptic rats.Methods A total of 208 21-d old SD rats were equally randomized into status epilepticusgroup (SE,n=96),normal control group (NS,n=96) and PD98059 (the ERKsignaling pathway specific inhibitor) treatment group (n=16),respectively; SE rat models of the SE group were induced by intraperitoneal injection of 1％ PTZ (80 mg/kg),and rats of the NS group received injection of normal saline (NS); 0.5,1,1.5,6,12 and 24 h after the inducement,the mRNA and protein expressions of HIF-lα and ERK1/2 in the hippocampus of rats in these two groups were examined by RT-PCR and Westem blotting.For rats in the PD98059 treatment group,PD98059 was intraperitoneally injected 10 minutes before intraperitoneal injection of pentylenetetrazol; 1 h after the inducement,the mRNA expressions of HIF-1α and ERK1/2 in the hippocampus of rats were examined by RT-PCR,while 1.5 h after the inducement,the protein expressions of HIF-1α and ERK1/2 in the hippocampus of rats were examined by Western blotting.The results of the PD98059 treatment group would be compared with those of the SE group.Results Compared with the NS group,the mRNA and protein expressions of HIF-1α and ERK 1/2 in the hippocampus of rats in the SE group after SE increased significantly; the peakexpression time ofERK1/2 mRNA was 1 h after SE (1.112±0.126 h),and the ERK1/2 protein mostly expressed at 1.5 h after SE (1.127±0.155 h).As to HIF-1α mRNA and its protein,the peak expression time was 1.5 h after SE (0.589±0.090 h) and 6 h after SE (0.230±0.052 h),respectively (P＜0.05).Compared with the SE group,the mRNA and protein expressions of HIF-1α and ERK1/2 in the hippocampus of all the rats in the PD98059 treatment group after SE decreased significantly (P＜0.05);positive correlation between HIF-1α and ERK1/2 mRNA in the SE group was noted (r=0.688,P=0.000).Conclusion ERK signaling pathway is activated in the epileptic rats and it participates in the expressionof HIF-1α in the hippocampus. Key words: Status epilepticus; Hippocampus; Extracellular signal-regulated kinase1/2; Hypoxia-inducible factor-1α