Melatonin Mediates Protective Effects against Kainic Acid-Induced Neuronal Death through Safeguarding ER Stress and Mitochondrial Disturbance.
Melatonin Mediates Protective Effects against Kainic Acid-Induced Neuronal Death through Safeguarding ER Stress and Mitochondrial Disturbance.
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褪黑激素通过保护内质网应激和线粒体紊乱来介导针对红藻氨酸诱导的神经元死亡的保护作用
DOI：
10.3389/fnmol.2017.00049
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发表时间：
2017
影响因子：
4.8
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Xue F;Shi C;Chen Q;Hang W;Xia L;Wu Y;Tao SZ;Zhou J;Shi A;Chen J
红藻氨酸(KA)诱导的神经元死亡与线粒体功能障碍和内质网应激有关。已知褪黑素可以保护海马神经元免受KA诱导的细胞凋亡，但褪黑素保护神经元线粒体紊乱和内质网应激的确切机制仍不清楚。在这项研究中，我们通过线粒体功能障碍和内质网应激介导的信号通路来研究褪黑素在KA诱导的细胞凋亡中的保护作用。KA通过激活钙蛋白酶导致线粒体动力学紊乱和功能障碍，导致神经元凋亡。Ca~(2+)螯合剂BAPTA-AM和钙蛋白酶抑制剂CalPeptin能显着恢复线粒体的形态和功能。KA处理也可诱导内质网应激。内质网应激抑制剂4-苯丁酸(PBA)可减轻内质网应激诱导的细胞凋亡和线粒体紊乱。值得注意的是，在PBA的作用下，Calain的激活也被抑制。因此，我们得出结论，褪黑素通过减轻钙超载和内质网应激，有效地抑制KA诱导的钙蛋白上调/激活和线粒体恶化。
Kainic acid (KA)-induced neuronal death is linked to mitochondrial dysfunction and ER stress. Melatonin is known to protect hippocampal neurons from KA-induced apoptosis, but the exact mechanisms underlying melatonin protective effects against neuronal mitochondria disorder and ER stress remain uncertain. In this study, we investigated the sheltering roles of melatonin during KA-induced apoptosis by focusing on mitochondrial dysfunction and ER stress mediated signal pathways. KA causes mitochondrial dynamic disorder and dysfunction through calpain activation, leading to neuronal apoptosis. Ca2+ chelator BAPTA-AM and calpain inhibitor calpeptin can significantly restore mitochondrial morphology and function. ER stress can also be induced by KA treatment. ER stress inhibitor 4-phenylbutyric acid (PBA) attenuates ER stress-mediated apoptosis and mitochondrial disorder. It is worth noting that calpain activation was also inhibited under PBA administration. Thus, we concluded that melatonin effectively inhibits KA-induced calpain upregulation/activation and mitochondrial deterioration by alleviating Ca2+ overload and ER stress.