Inhibition of cerebral ischemia/reperfusion-induced injury by adenovirus expressed C-terminal amino acids of GluR6.

Abstract

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.

• Authors: Ting Li, Hong-Min Yu, Ya-Feng Sun, Yuan-Jian Song, Guang-Yi Zhang, Dong-Sheng Pei
• Journal: Brain research (Brain Res) Vol. 1300 Pg. 169-76 (Dec 01 2009) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 19747468 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Disks Large Homolog 4 Protein
• Dlg4 protein, rat
• Gluk2 kainate receptor
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins
• Receptors, Kainic Acid
• Mitogen-Activated Protein Kinase 10
• MAP Kinase Kinase Kinases
• mitogen-activated protein kinase kinase kinase 11

Topics

• Adenoviridae (metabolism)
• Analysis of Variance
• Animals
• Blotting, Western
• Brain Ischemia (metabolism, pathology, therapy)
• CA1 Region, Hippocampal (metabolism, pathology)
• Cell Death (physiology)
• Cell Fractionation
• Cell Survival (genetics)
• Cytoprotection
• Disks Large Homolog 4 Protein
• Gene Transfer Techniques
• Genetic Vectors
• Intracellular Signaling Peptides and Proteins (metabolism)
• MAP Kinase Kinase Kinases (metabolism)
• Male
• Membrane Proteins (metabolism)
• Mitogen-Activated Protein Kinase 10 (metabolism)
• Neurons (metabolism)
• Phosphorylation
• Rats
• Rats, Sprague-Dawley
• Receptors, Kainic Acid (metabolism)
• Reperfusion Injury (metabolism, pathology, therapy)
• Signal Transduction (physiology)
• Staining and Labeling
• Subcellular Fractions (metabolism)