Phosphorylation of neuronal nitric oxide synthase at Ser847 in the nucleus intermediolateralis after spinal cord injury in mice
Phosphorylation of neuronal nitric oxide synthase at Ser847 in the nucleus intermediolateralis after spinal cord injury in mice
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DOI：
10.1016/j.neuroscience.2006.10.034
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发表时间：
2007-03-02
期刊：
影响因子：
3.3
通讯作者：
Yoshida, J.
中科院分区：
文献类型：
--
作者：
Osuka, K.;Watanabe, Y.;Yoshida, J.
我们以前证明，钙离子/钙调素（CaM）依赖性蛋白激酶II α（CaM-KII α）可以磷酸化神经元一氧化氮合酶（nNOS）在Ser（847）和减弱NOS活性在神经元细胞。在本研究中，我们集中在小鼠脊髓损伤（SCI）后nNOS，磷酸化（p）-Ser（847）-nNOS（NP 847），CaM-KII和p-Thr（286）-CaM-KII α水平和细胞定位的时间变化。Western blot分析显示，nNOS在脊髓损伤后3 h开始在Ser（847）处磷酸化，24 h达到峰值，此后逐渐下降，CaM-K Ⅱ与nNOS共定位。免疫组织化学分析显示，脊髓损伤引起的增加，在NP 847和p-Thr（286）-CaM-KII α在中间外侧核。这些发现表明SCI诱导p-Thr（286）-CaM-KII α，其使中间外侧核中Ser（847）处的nNOS磷酸化，其中NO被认为在自主节前神经元中作为神经递质发挥作用。因此，NP 847信号通路可能参与了SCI后立即发生的自主神经功能衰竭。(c)2006年IBRO。由爱思唯尔有限公司出版。保留所有权利。
We previously demonstrated that Ca2+/calmodulin (CaM)-dependent protein kinase II alpha (CaM-KII alpha) can phosphorylate neuronal nitric oxide synthase (nNOS) at Ser(847) and attenuate NOS activity in neuronal cells. In the present study we focused on chronological alteration in levels and cellular location of nNOS, phosphorylated (p)-Ser(847)-nNOS (NP847), CaM-KII and p-Thr(286)-CaM-KII alpha following spinal cord injury (SCI) in mice. Western blot analysis showed nNOS to be significantly phosphorylated at Ser(847) from 3 h after SCI, peaking at 24 h and gradually decreasing thereafter, and CaM-KII to be colocalized with nNOS after SCI. Immunohistochemical analysis revealed that SCI causes an increase in both NP847 and p-Thr(286)-CaM-KII alpha in the nucleus intermediolateralis. These findings suggest that SCI induces p-Thr(286)-CaM-KII alpha, which phosphorylates the nNOS at Ser(847) in the nucleus intermediolateralis where NO is thought to play a role as a neurotransmitter in autonomic preganglionic neurons. Thus, the NP847 signaling pathway might be involved in the autonomic failure which occurs immediately after SCI. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.