短暂性全脑缺血可增强大鼠海马CA1区α-氨基-3-羟基-5-甲基异恶唑-4-丙酸受体GluR1亚基的磷酸化。

Transient global ischemia enhances phosphorylation of the GluR1 subunit of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor in the hippocampal CA1 region in rats.

作者信息

Takagi Yuko, Takagi Norio, Besshoh Shintaro, Miyake-Takagi Keiko, Takeo Satoshi

机构信息

Faculty of Pharmaceutical Sciences, Department of Pharmacology, Tokyo University of Pharmacy & Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.

出版信息

Neurosci Lett. 2003 Apr 24;341(1):33-6. doi: 10.1016/s0304-3940(03)00153-8.

DOI:10.1016/s0304-3940(03)00153-8

Abstract

Phosphorylation of the GluR1 subunit of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor has been implicated in the regulation of the receptor channel. We investigated the effects of transient global ischemia in rats on phosphorylation of the GluR1 subunit in the hippocampal CA1 and CA3/dentate gyrus. Transient ischemia induced an increase in the phosphorylation of GluR1 at Ser831 in the CA1 at 1 h of reperfusion. In contrast, the phosphorylation of Ser845 in neither region was affected by the ischemia. The amounts of calcium/calmodulin-dependent kinase (CaMKII) and its activated form, but not cAMP-dependent protein kinase subunits, were increased in a crude membrane fraction after ischemia. The results suggest that an activated CaMKII may phosphorylate Ser831 of GluR1 and a consequent phosphorylation of GluR1 may be related to pathogenic events occurring in the vulnerable subfield of the hippocampus after transient global ischemia.

摘要

α-氨基-3-羟基-5-甲基异恶唑-4-丙酸受体的GluR1亚基磷酸化与受体通道的调节有关。我们研究了大鼠短暂性全脑缺血对海马CA1区和CA3/齿状回中GluR1亚基磷酸化的影响。短暂性缺血在再灌注1小时时诱导CA1区GluR1在Ser831位点的磷酸化增加。相比之下，两个区域中Ser845的磷酸化均不受缺血影响。缺血后粗制膜组分中钙/钙调蛋白依赖性激酶（CaMKII）及其活化形式的量增加，但cAMP依赖性蛋白激酶亚基的量未增加。结果表明，活化的CaMKII可能使GluR1的Ser831位点磷酸化，GluR1随后的磷酸化可能与短暂性全脑缺血后海马易损亚区发生的致病事件有关。