Functional cooperation between KA2 and GluR6 subunits is involved in the ischemic brain injury

• Published in: Journal of neuroscience research Vol. 85; no. 13; pp. 2960 - 2970
• Main Authors: Jiang, Hai-Xia, Guan, Qiu-Hua, Pei, Dong-Sheng, Zhang, Guang-Yi
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.10.2007
• Subjects: Animals; Brain Ischemia - drug therapy; Brain Ischemia - metabolism; Brain Ischemia - pathology; Cell Death - drug effects; Disks Large Homolog 4 Protein; GluK2 Kainate Receptor; GluR6; Hippocampus - drug effects; Hippocampus - pathology; In Situ Nick-End Labeling - methods; Injections, Intraventricular; Intracellular Signaling Peptides and Proteins - metabolism; ischemic brain injury; JNK; KA2; Male; MAP Kinase Kinase Kinases - metabolism; Membrane Proteins - metabolism; Mitogen-Activated Protein Kinase Kinase Kinase 11; Oligodeoxyribonucleotides, Antisense - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Kainic Acid - chemistry; Receptors, Kainic Acid - metabolism; Reperfusion - methods; Signal Transduction - drug effects; Signal Transduction - physiology; Time Factors
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.21334

We investigated the possible relationships between KA2 subunit and GluR6 subunit, as well as the role of KA2 subunit in neuronal death induced by cerebral ischemia/reperfusion. Our results indicated that intracerebroventricular infusion of KA2 antisense oligodeoxynucleotides (AS) not only knocked down the expressions of KA2 and GluR6, but also suppressed the assembly of the GluR6/KA2‐PSD95‐MLK3 signaling module, and inhibited JNK activation and phosphorylation of c‐jun. In addition, infusion of KA2 AS increased neuronal survival in CA1 region after 5 days of reperfusion. More interestingly, we found that the combination of KA2 and GluR6 AS exerted more significant effects than when pretreated with KA2 AS or GluR6 AS alone. Our results suggest that the KA2 subunit is involved in delayed neuronal death induced by cerebral ischemia, at the same time, it is noteworthy that the functional cooperation between KA2 and GluR6 subunits plays a critical role in the ischemic brain injury by PSD95‐MLK3‐MKK4/7‐JNK3 signal pathway. © 2007 Wiley‐Liss, Inc.