Presynaptic Caytaxin prevents apoptosis via deactivating DAPK1 in the acute phase of cerebral ischemic stroke
Presynaptic Caytaxin prevents apoptosis via deactivating DAPK1 in the acute phase of cerebral ischemic stroke
复制标题
突触前 Caytaxin 通过在脑缺血性卒中急性期失活 DAPK1 来预防细胞凋亡
DOI：
10.1016/j.expneurol.2020.113303
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发表时间：
2020-07-01
影响因子：
5.3
通讯作者：
Pei，Lei
中科院分区：
文献类型：
--
作者：
Wang，Shan;Chen，Keng;Pei，Lei
死亡相关蛋白激酶1（DAPK 1）是介导缺血性卒中神经元死亡的关键蛋白。虽然DAPK 1的作用底物及在脑卒中中的分子信号已逐渐被发现，但DAPK 1本身的调节作用尚不清楚。在这里，我们首次揭示，Caytaxin，BCL 2/腺病毒E1 B相互作用蛋白（BNIP-2）的脑特异性成员，增加和DAPK 1相互作用，早在大脑中动脉闭塞（MCAO）后2小时，在小鼠大脑的半影区。此外，Caytaxin在突触前位点与DAPK 1结合并抑制DAPK 1催化活性。通过Caytaxin shRNA沉默Caytaxin（Sh-Caytaxin）增强DAPK 1活性，在体内和体外均加重神经元凋亡和脑损伤。因此，升高突触前Caytaxin可通过抑制缺血性卒中急性期DAPK 1活化来防止神经元凋亡。Caytaxin对神经细胞具有生理保护作用，是缺血性脑卒中早期预防和治疗的潜在靶点。
Death-associated protein kinase 1 (DAPK1) is a key protein that mediates neuronal death in ischemic stroke. Although the substrates of DAPK1 and molecular signal in stroke have been gradually discovered, the modulation of DAPK1 itself is still unclear. Here we first reveal that Caytaxin, a brain-specific member of BCL2/adenovirus E1B -interacting protein (BNIP-2), increases and interacts with DAPK1 as early as 2 h after middle cerebral artery occlusion (MCAO) in the penumbra area of mouse brain. Furthermore, Caytaxin binds to DAPK1 at the presynaptic site and inhibits DAPK1 catalytic activity. Silencing Caytaxin by Caytaxin shRNA (Sh-Caytaxin) enhances DAPK1 activity, deteriorates neuronal apoptosis and brain injuries bothin vivoandin vitro. Thus, elevating presynaptic Caytaxin could prevent neuronal apoptosis by inhibiting DAPK1 activation in the acute stage of ischemic stroke. Caytaxin may physiologically protect neuronal cells and represent a potential prevention and therapeutic target in the early phase of cerebral ischemic stroke.