Involvement of calcium/calmodulin-dependent protein kinase II in methamphetamine-induced neural damage

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• 作者：Xufeng Chen ; Jingjing Xing ; Lei Jiang ; Wenyi Qian ; Yixin Wang ; Hao Sun ; Yu Wang ; Hang Xiao ; Jun Wang and Jinsong Zhang
• 刊名：Journal of Applied Toxicology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：36
• 期：11
• 页码：1460-1467
• 全文大小：888K
• ISSN：1099-1263

文摘

Methamphetamine (METH), an illicit drug, is widely abused in many parts of the world. Mounting evidence shows that METH exposure contributes to neurotoxicity, particularly for the monoaminergic neurons. However, to date, only a few studies have tried to unravel the mechanisms involved in METH-induced non-monoaminergic neural damage. Therefore, in the present study, we tried to explore the mechanisms for METH-induced neural damage in cortical neurons. Our results showed that METH significantly increased intracellular [Ca²⁺]_i in Ca²⁺-containing solution rather than Ca²⁺-free solution. Moreover, METH also upregulated calmodulin (CaM) expression and activated CaM-dependent protein kinase II (CaMKII). Significantly, METH-induced neural damage can be partially retarded by CaM antagonist W7 as well as CaMKII blocker KN93. In addition, L-type Ca²⁺ channel was also proved to be involved in METH-induced cell damage, as nifedipine, the L-type Ca²⁺ channel-specific inhibitor, markedly attenuated METH-induced neural damage. Collectively, our results suggest that Ca²⁺-CaM-CaMKII is involved in METH-mediated neurotoxicity, and it might suggest a potential target for the development of therapeutic strategies for METH abuse. Copyright