[CREB activation is a key player for ischemic tolerance in the brain].
[CREB activation is a key player for ischemic tolerance in the brain].
复制标题
[CREB 激活是大脑缺血耐受的关键因素]。
DOI：
10.5692/clinicalneurol.52.904
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
H. Mochizuki
中科院分区：
文献类型：
--
作者：
K. Kitagawa;Tsutomu Sasaki;Y. Terasaki;Y. Yagita;H. Mochizuki
缺血耐受对于神经保护和低温一样强大和可重复。几种途径可能参与缺血耐受的获得。CREB是脑内含量丰富的转录因子，在突触可塑性和神经元存活中起着重要作用。CREB激活也被证明参与缺血耐受。缺血或氧-葡萄糖剥夺导致谷氨酸的释放，其结合突触NMDA受体。然后，钙离子流入细胞内空间激活钙-钙调蛋白依赖性蛋白激酶（CaMK）。CaMK I/IV磷酸化CREB的Ser 133和盐诱导激酶（SIK）的Thr 484。SIK 2在Thr 484处的磷酸化通过泛素蛋白酶体系统触发SIK 2的降解。SIK 2维持CREB调节的转录辅激活因子（CRTC）的磷酸化水平。SIK 2的降解诱导CRTC 1的去磷酸化，并将CRTC 1从细胞质移动到细胞核中。因此，CRTC 1结合CREB的基本ZIP结构域。Ser 133磷酸化和结合到CREB的基本ZIP结构域的CRTC 1都增强了CREB介导的转录，诱导存活因子的基因表达，并使神经元对随后的严重缺血具有抗性。
Ischemic tolerance is as powerful and reproducible for neuro-protection as hypothermia. Several pathways could be involved in acquisition of ischemic tolerance. CREB is an abundant transcription factor in the brain and plays critical role on synaptic plasticity and neuronal survival. CREB activation has been also shown to be involved in ischemic tolerance. Ischemia or oxygen-glucose deprivation leads to release of glutamate, which binds to synaptic NMDA receptor. Then, influx of calcium ions into intracellular space activates calcium-calmodulin dependent protein kinase (CaMK). CaMK I/IV phosphorylates Ser 133 of CREB, and Thr 484 of salt-inducible kinase (SIK). Phosphorylation of SIK2 at Thr 484 triggers degradation of SIK2 through ubiquitin proteasome system. SIK2 maintains the phosphorylation level of CREB-regulated transcriptional co-activator (CRTC). Degradation of SIK2 induces dephosphorylation of CRTC1, and moves CRTC1 from cytoplasm into nucleus. Thus CRTC1 binds to basic ZIP domain of CREB. Both Ser133 phosphorylation and CRTC1 bound to the basic ZIP domain of CREB enhances CRE-mediated transcription, induces gene expression of survival factors, and renders the neurons resistant to subsequent severe ischemia.
影响因子：
6.3
作者：
Y. Terasaki;Tsutomu Sasaki;Y. Yagita;Shuhei Okazaki;Y. Sugiyama;N. Oyama;E. Omura-Matsuoka;S. Sakoda-S.
通讯作者：
Y. Terasaki;Tsutomu Sasaki;Y. Yagita;Shuhei Okazaki;Y. Sugiyama;N. Oyama;E. Omura-Matsuoka;S. Sakoda-S.
小鼠局灶性脑缺血后梗塞笔区 CRE 介导的基因转录
DOI：
--
发表时间：
2004
期刊：
Journal of Neuroscience Research 75
影响因子：
--
作者：
Yazaki M;Hashikura Y;Takei Y;Ikegami T;Miyagawa S;Yamamoto K;Tokuda T;Kobayashi K;Saheki T;Ikeda S;Shiro Sugiura
通讯作者：
Shiro Sugiura