Neural Regeneration Research ›› 2013, Vol. 8 ›› Issue (2): 111-120.doi: 10.3969/j.issn.1673-5374.2013.02.002

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The calmodulin-dependent protein kinase II inhibitor KN-93 protects rat cerebral cortical neurons from N-methyl-D-aspartic acid-induced injury

Xuewen Liu1, Cui Ma2, Ruixian Xing1, Weiwei Zhang3, Buxian Tian1, Xidong Li1, Qiushi Li1,   Yanhui Zhang1
  

  1. 1 Department of Neurology, First Affiliated Hospital of Liaoning Medical College, Jinzhou 121001, Liaoning Province, China
    2 Liaoning Medical College, Jinzhou 121001, Liaoning Province, China
    3 Jinzhou Kangning Hospital, Jinzhou 121001, Liaoning Province, China
  • Received:2012-06-18 Revised:2012-09-13 Online:2013-01-15 Published:2013-01-15
  • Contact: Xuewen Liu, Department of Neurology, First Affiliated Hospital of Liaoning Medical College, Jinzhou 121001, Liaoning Province, China,sjnklxw@163.com.
  • About author:Xuewen Liu☆, M.D., Chief physician.
  • Supported by:

    This study was supported by Liaoning Social Development Key Projects of Scientific and Technological Department of Liaoning Province, No. 2012225019.

Abstract:

In this study, primary cultured cerebral cortical neurons of Sprague-Dawley neonatal rats were treated with 0.25, 0.5, and 1.0 μM calmodulin-dependent protein kinase II inhibitor KN-93 after    50 μM N-methyl-D-aspartic acid-induced injury. Results showed that, compared with N-methyl-D- aspartic acid-induced injury neurons, the activity of cells markedly increased, apoptosis was significantly reduced, leakage of lactate dehydrogenase decreased, and intracellular Ca2+ concentrations in neurons reduced after KN-93 treatment. The expression of caspase-3, phosphorylated calmodulin-dependent protein kinase II and total calmodulin-dependent protein kinase II protein decreased after KN-93 treatment. And the effect was apparent at a dose of 1.0 μM KN-93. Experimental findings suggest that KN-93 can induce a dose-dependent neuroprotective effect, and that the underlying mechanism may be related to the down-regulation of caspase-3 and calmodulin- dependent protein kinase II expression.

Key words: neural regeneration, brain injury, calmodulin-dependent protein kinase II, KN-93, N-methyl-D- aspartic acid, caspase-3, calcium ion, apoptosis, neuroprotection, grant-supported paper, photographs-containing paper, neuroregeneration