NMDA receptor-mediated immediate Ser831 phosphorylation of GluR1 through CaMKIIα in rat hippocampus during early global ischemia
NMDA receptor-mediated immediate Ser831 phosphorylation of GluR1 through CaMKIIα in rat hippocampus during early global ischemia
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DOI：
10.1016/j.neures.2003.09.009
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发表时间：
2004-01-01
影响因子：
2.9
通讯作者：
Zhang, GY
中科院分区：
文献类型：
--
作者：
Fu, XZ;Zhang, QG;Zhang, GY
α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）受体亚基GluR 1在Ser 831位的磷酸化参与AMPA受体通道的调节。本研究观察了大鼠海马GluR 1的Ser 831磷酸化，发现全脑缺血早期GluR 1磷酸化明显增加。为了进一步阐明潜在的机制，钙/钙调蛋白依赖性激酶II α（CaMKII alpha）抑制剂1-[N，O-双-（5-异喹啉磺酰基）-N-甲基-L-酪氨酰基]-4-苯基哌嗪（KN 62）、CaM拮抗剂三氟拉嗪（TFP）、N-甲基-D-天冬氨酸（NMDA）受体拮抗剂美沙芬（DEX）、AMPA受体拮抗剂6，7-二硝基喹喔啉-2，3-（1H，4 H）-二酮（DNQX）和L型电压门控性钙通道（L-VGCC）阻断剂硝苯地平（NIF）。结果表明，KN 62、TFP和DEX均能显著抑制GluR I的Ser 831磷酸化。而DNQX和NIF则无明显作用。因此，这些研究表明，早期全脑缺血诱导的GluR 1的Ser 831磷酸化可能与CaMK II α和NMDA受体密切相关，而GluR I的立即Ser 831磷酸化可能参与了早期全脑缺血后的致病事件。(C)2003年爱思唯尔爱尔兰有限公司和日本神经科学学会。All rights reserved.
The phosphorylation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors subunit GluR1 at Ser831 has been implicated in the regulation of AMPA receptors channel. In this paper, Ser831 phosphorylation of GluR1 in rat hippocampus was investigated, which significantly increased during early global ischemia. To further illustrate the underlying mechanisms, calcium/calmodulin-dependent kinase IIalpha (CaMKIIalpha) inhibitor 1-[N,O-bis-(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN62), CaM antagonist trifluoperazine (TFP), N-methyl-D-aspartate (NMDA) receptor antagonist dextromethorphan (DEX), AMPA receptor antagonist 6,7-dinitroquinoxaline-2,3-(1H,4H)-dione (DNQX) and L-type voltage-gated Ca2+ channel (L-VGCC) blocker nifedipine (NIF), were respectively administrated to the rats 20 min prior to ischemia. The results showed that KN62, TFP and DEX significantly attenuated Ser831 phosphorylation of GluR I. while DNQX and NIF had no obvious effects. Consequently, the studies suggest that early global ischemia induced Ser831 phosphorylation of GluR1 may be closely associated with CaMKIIalpha and the NMDA receptor, while the immediate Ser831 phosphorylation of GluR I may have been involved in pathogenic events after early global ischemia. (C) 2003 Elsevier Ireland Ltd and The Japan Neuroscience Society. All rights reserved.