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

Xuewen Liu; Cui Ma; Ruixian Xing; Weiwei Zhang; Buxian Tian; Xidong Li; Qiushi Li; Yanhui Zhang

doi:10.3969/j.issn.1673-5374.2013.02.002

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

Neural Regen Res. 2013 Jan 15;8(2):111-20. doi: 10.3969/j.issn.1673-5374.2013.02.002.

Authors

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

Affiliations

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.

PMID: 25206480
PMCID: PMC4107511
DOI: 10.3969/j.issn.1673-5374.2013.02.002

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-Daspartic acid-induced injury neurons, the activity of cells markedly increased, apoptosis was significantly reduced, leakage of lactate dehydrogenase decreased, and intracellular Ca(2+) 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.

Keywords: KN-93; N-methyl-Daspartic acid; apoptosis; brain injury; calcium ion; calmodulin-dependent protein kinase II; caspase-3; grant-supported paper; neural regeneration; neuroprotection; neuroregeneration; photographs-containing paper.