Inhibition of cerebral ischemia/reperfusion-induced injury by adenovirus expressed C-terminal amino acids of GluR6.
GluR6 kainate receptor subunit is largely expressed in hippocampus of brain regions and plays an important role in brain ischemia/reperfusion-mediated neuronal cell death. Our previous researches have shown that cerebral ischemia/reperfusion could facilitate the assembly of GluR6 and postsynaptic density protein 95(PSD95) as well as mixed lineage kinase 3(MLK3) and further induce the activation of c-Jun NH2-terminal kinase 3(JNK3), leading to neuronal death of hippocampal CA1. Here, we show that over-expression of C-terminal amino acids of GluR6 can interrupt the combination of GluR6 with PSD95, inhibit the assembly of GluR6.PSD-95.MLK3 signaling module, suppress the activation of JNK3 and the downstream signaling pathway. Thus, our results imply that over-expression of C-terminal amino acids of GluR6 induce neuroprotection against ischaemic brain injury in rat hippocampal CA1 region via suppressing proapoptosis signaling pathways, which can be an experimental foundation for gene therapy of stroke.
Li
Ting
T
Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, Xuzhou 221002, China.
Yu
Hong-Min
HM
Sun
Ya-Feng
YF
Song
Yuan-Jian
YJ
Zhang
Guang-Yi
GY
Pei
Dong-Sheng
DS
D000256:Adenoviridae / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000502:physiology; D002458:Cell Fractionation; D002470:Cell Survival / Q000235:genetics; D019610:Cytoprotection; D000076122:Disks Large Homolog 4 Protein; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015398:Signal Transduction / Q000502:physiology; D013194:Staining and Labeling; D013347:Subcellular Fractions / Q000378:metabolism; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11; D000097806:GluK2 Kainate Receptor
D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D008565:Membrane Proteins; D048057:Mitogen-Activated Protein Kinase 10; D018092:Kainic Acid Receptors; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11; D000097806:GluK2 Kainate Receptor; C501449:Dlg4 protein, rat