Meng Fanjie, Zhang Guangyi
Research Center of Biochemistry and Molecular Biology, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou 221002, Jiangsu, People's Republic of China.
Neurosci Lett. 2002 Nov 15;333(1):59-63. doi: 10.1016/s0304-3940(02)00961-8.
In this article, we investigated the autophosphorylation and translocation of calcium/calmodulin-dependent protein kinase II alpha (CaMKII alpha) in hippocampus during global ischemia. The following results were observed: (1) CaMKII alpha immediately became autophosphorylated after 3 min ischemia, at the same time, there is a dramatic and sustained translocation of CaMKII alpha from cytosolic fraction to synaptic fraction; (2) CaMKII alpha translocated to post-synaptic density and targeted N-methyl-D-aspartate receptor subunit 2B (NR2B) which was serine-phosphorylated by active CaMKII alpha; (3) serine phosphorylation of NR2B could not only inhibit the formation of CaMKII alpha-NR2B complexes but also promote the dissociation of the preformed complexes when ischemic time was prolonged. These results suggest that phosphorylation of NR2B can influence the channel properties of NR2B, and the dissociation of the CaMKII alpha-NR2B complexes may be a negative feedback mechanism during longer time cerebral ischemia.
在本文中，我们研究了全脑缺血期间海马体中钙/钙调蛋白依赖性蛋白激酶IIα（CaMKIIα）的自磷酸化和转位情况。观察到以下结果：（1）缺血3分钟后，CaMKIIα立即发生自磷酸化，与此同时，CaMKIIα从胞质组分向突触组分发生显著且持续的转位；（2）CaMKIIα转位至突触后致密区并靶向N-甲基-D-天冬氨酸受体亚基2B（NR2B），该亚基被活性CaMKIIα丝氨酸磷酸化；（3）当缺血时间延长时，NR2B的丝氨酸磷酸化不仅可抑制CaMKIIα-NR2B复合物的形成，还能促进已形成复合物的解离。这些结果表明，NR2B的磷酸化可影响NR2B的通道特性，且CaMKIIα-NR2B复合物的解离可能是长时间脑缺血期间的一种负反馈机制。
