Signal transducers and activators of transcription 5 contributes to erythropoietin-mediated neuroprotection against hippocampal neuronal death after transient global cerebral ischemia
Signal transducers and activators of transcription 5 contributes to erythropoietin-mediated neuroprotection against hippocampal neuronal death after transient global cerebral ischemia
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信号转导器和转录激活剂 5 有助于促红细胞生成素介导的神经保护，防止短暂性全脑缺血后海马神经元死亡
DOI：
10.1016/j.nbd.2006.08.007
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发表时间：
2007-01
影响因子：
6.1
通讯作者：
Chen, Jun
中科院分区：
文献类型：
--
作者：
Gao, Yanqin;Zhang, Feng;Cao, Guodong;Wang, Suping;Chen, Jun
信号转导和转录激活因子（STAT）蛋白是一类转录因子。其中，STAT 5启动促存活信号级联。到目前为止，对STAT 5在脑缺血和再灌注中的作用知之甚少。本研究探讨了大鼠短暂性全脑缺血后早期海马CA 1区STAT 5的磷酸化状态。我们的数据表明，在海马CA 1区的STAT 5磷酸化增加，在1h和3 h缺血。利用促红细胞生成素（EPO）在CA 1中的神经保护作用，我们进一步证明了EPO的施用增强了STAT 5的磷酸化，其中SATA 5a更早地被磷酸化。EPO处理组中STAT 5磷酸化的增强伴随着STAT 5下游基因产物Bcl-xL和XIAP的上调。因此，缺血性CA 1神经元损伤减弱EPO的管理。STAT 5磷酸化的增强和EPO提供的神经保护都被Tyrphostin阻断，Tyrphostin是Janus激酶2的选择性抑制剂，Janus激酶2是STAT 5的上游激酶。这些发现表明，脑缺血后STAT 5的激活和CA 1神经元存活之间的关联。
The signal transducers and activators of transcription (STAT) proteins are a group of transcriptional factors. Among them, STAT5 initiates a pro-survival signaling cascade. So far, little has been known about the role of STAT5 in cerebral ischemia and reperfusion. This study examines the phosphorylation status of STAT5 in hippocampal CA1 in the early stage after transient global cerebral ischemia in rats. Our data show that the phosphorylation of STAT5 was increased in hippocampal CA1 at 1h and 3h ischemia. Taking advantage of the neuroprotective effect of erythropoietin (EPO) in CA1, we further demonstrated that the administration of EPO enhanced the phosphorylation of STAT5, with SATA5a being phosphorylated earlier. The enhanced phosphorylation of STAT5 in the EPO-treated group was accompanied by the upregulation of STAT5 downstream gene products, Bcl-xL and XIAP. Consequently, ischemic CA1 neuronal damage was attenuated by the administration of EPO. Both the enhancement of STAT5 phosphorylation and the neuroprotection rendered by EPO were blocked by Tyrphostin, a selective inhibitor for Janus kinase 2, which is an upstream kinase of STAT5. These findings suggest an association between the activation of STAT5 and CA1 neuronal survival after cerebral ischemia.
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影响因子：
11.2
作者：
S. Mohapatra;B. Chu;Sheng Wei;J. Djeu;P. Epling-Burnette;T. Loughran;R. Jove;W. J. Pledger
通讯作者：
S. Mohapatra;B. Chu;Sheng Wei;J. Djeu;P. Epling-Burnette;T. Loughran;R. Jove;W. J. Pledger
影响因子：
5
作者：
Catania, MA;Marciano, MC;Calapai, G
通讯作者：
Calapai, G
影响因子：
5.3
作者：
Ruscher, K;Freyer, D;Meisel, A
通讯作者：
Meisel, A
影响因子：
64.5
作者：
Parganas, E;Wang, D;Ihle, JN
通讯作者：
Ihle, JN
影响因子：
4.7
作者：
Nagayama, T;Lan, J;Chen, J
通讯作者：
Chen, J