title: Involvement of calcium/calmodulin-dependent protein kinase II in methamphetamine-induced neural damage.
abstract: 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 [Ca(2) (+) ]i in Ca(2) (+) -containing solution rather than Ca(2) (+) -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 Ca(2) (+) channel was also proved to be involved in METH-induced cell damage, as nifedipine, the L-type Ca(2) (+) channel-specific inhibitor, markedly attenuated METH-induced neural damage. Collectively, our results suggest that Ca(2) (+) -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 © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Emergency Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Emergency Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Emergency Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan East Road, Nanjing, Jiangsu, 211166, China.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Qian
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan East Road, Nanjing, Jiangsu, 211166, China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Emergency Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan East Road, Nanjing, Jiangsu, 211166, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan East Road, Nanjing, Jiangsu, 211166, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan East Road, Nanjing, Jiangsu, 211166, China. wangjun@njmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Emergency Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China. zhangjsojz@126.com.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008694:Methamphetamine / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D017207:Rats, Sprague-Dawley
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium
keywords: CaM; CaMKII; L-type Ca2+ channel; Methamphetamine; neural damage