Protective effect of GluR6-9c peptide containing TAT protein on hippocampus CA1 region neuronal cell injury in rats with ischemic brain injury through inhibiting MLK3-MKK7-JNK signal transduction pathway / 中华神经医学杂志

ABSTRACT

Objective To investigate the effect of peptide Tat-GluR6-9c on phosphorylations and protein expressions of mixed-lineage kinase 3 (MLK3),mitogen-activated protein kinase kinase 7 (MKK7) and c-Jun NH2-terminal kinase (JNK),and its effect on hippocampus CA1 region neuronal cell injury induced by cerebral ischemia followed by reperfusion.Methods Twenty four adult male SD rats were randomly divided into sham-operated group,ischemia-reperfusion group (I/R),Tat-GluR6-AA treatment group and Tat-GluR6-9c treatment group (n=6).Four-vessel occlusion method was employed to establish the cerebral ischemia models in the later 3 groups.The effects of peptide Tat-GluR6-9c on the phosphorylations and protein expressions of MLK3 (6 h after the reperfusion) and JNK (3 d after the reperfusion) were detected by Western blotting; the effects ofpeptide Tat-GluR6-9c on the phosphorylation and protein expression of MLK7 (1 d after the reperfusion) were detected by Western blotting and immunohistochemistry.Cresyl Violet (CV) staining was employed to examine the survival of CA1 pyramidal cells in the hippocampus.Results The phosphorylation of MLK3,MKK7 and JNK in Tat-GluR6-9c treatment group was significantly less than that in I/R group and Tat-GluR6-AA treatment group (P＜0.05).As compared with I/R group and Tat-GluR6-AA group,peptide Tat-GluR6-9c group could obviously increase the number of neuron cells (P＜0.05).Conclusion Peptide Tat-GluR6-9c has a protective effect on neuron in CA1 region of hippocampus following cerebral ischemia-reperfusion by significantly decreasing the phosphorylations ofMLK3,MKK7 and JNK.