期刊
FRONTIERS IN MOLECULAR NEUROSCIENCE
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnmol.2017.00049
关键词
melatonin; kainic acid; cell death; mitochondrial dysfunction; endoplasmic reticulum stress
资金
- National Natural Science Foundation of China [31171027, 81371416, 31670778, 81371418, 31571466]
- Fundamental Research Funds for the Central Universities [HUST: 2016YXMS191, 2014YGYL005]
- Specialized Research Fund for the Doctoral Program of Higher Education [20130142110071]
- Program for New Century Excellent Talents in University [NCET-13-0234]
- Junior Thousand Talents Program of China
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.
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