Changes of protein kinase-like endoplasmic reticulum kinase and glucose-regulated protein 78 expression in rats after focal ischemic preconditioning

Yinling Hu ,Fang-Fang Bi ,Lei Ling ,Meizhen Zhu ,Nong Tang ,Yuying Hu

doi:10.3760/cma.j.issn.1006-7876.2012.01.012

Abstract

Objective To investigate the effect of focal ischemic preconditioning (IPC) on the expression of protein kinase-like endoplasmic reticulum kinase (PERK) and glucose-regulated protein 78 (GRP78) mRNA and protein after focal cerebral ischemia/reperfusion (I/R) in rats. Methods All 120 male SD rats were randomly divided into three groups: sham-operation group, middle cerebral artery occlusion (MCAO) group and brain ischemia preconditioning (BIP) group. Each group was further divided into 4 subgroups according to 12 h, 1, 2 and 3 d after I/R. The IPC models were made in order to measure the expression of PERK, GRP78 mRNA and protein by in situ hybridization and Western blot, and the apoptosis rate of neuron by flow cytometry. Results ①The expression of PERK mRNA increased and reached the peak at 12 h, then decreased continuously after 1 d. BIP could decrease its expression. The expression of PERK protein increased at 12 h and reached the peak at 24 h, then decreased continuously after 2 d. BIP could decrease its expression. ②The expression both of GRP78 mRNA and its protein all increased and reached the peak at 12 h, then decreased continuously. BIP could increase their expression (mRNA:12 h: 136.70±9.53, F=32.265; 24 h:147.54±9.97, F=54.920; 2 d:158.16±9.44, F=45.374; 3 d: 65.85±10.26, F=16.493, P<0.05; protein:12 h: 1.319±0.116, F=5.619, P<0.05; 24 h: 1.226±0.108, F=33.742, P<0.01; 2 d:1.183±0.112, F=46.556, P<0.01; 3 d: 1.115±0.098, F=11.730, P<0.05).③The rate of apoptosis neuron of rats in MCAO increased markedly at 12 h after reperfusion, and reached the peak at 1 d, then decreased continuously. BIP could decrease the rate of apoptosis neuron. Conclusion BIP can protect neurons through inhibiting the expression of PERK and inducing the expression of GRP78 after endoplasmic reticulum stress in rats. Key words: Brain ischemia; Ischemic preconditioning; eIF-2 Kinase; Heat-shock proteins; Rats

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