title: Melatonin Mediates Protective Effects against Kainic Acid-Induced Neuronal Death through Safeguarding ER Stress and Mitochondrial Disturbance.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, China; Department of Clinical Laboratory, Xi'an Third HospitalXi'an, China.
authors.forename: Feixiao
authors.initials: F
authors.lastname: Xue
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Weijian
authors.initials: W
authors.lastname: Hang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Liangtao
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of California Santa Barbara, Santa Barbara CA, USA.
authors.forename: Sophia Z
authors.initials: SZ
authors.lastname: Tao
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, China; Institute for Brain Research, Huazhong University of Science and TechnologyWuhan, China; Key Laboratory of Neurological Disease of National Education Ministry, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, China.
authors.forename: Anbing
authors.initials: A
authors.lastname: Shi
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, China; Institute for Brain Research, Huazhong University of Science and TechnologyWuhan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
keywords: cell death; endoplasmic reticulum stress; kainic acid; melatonin; mitochondrial dysfunction