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

摘要

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 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. Research Highlights KN-93, a calmodulin-dependent protein kinase II inhibitor, has a neuroprotective effect, and its underlying mechanism of action may be related to the down-regulation of caspase-3 and calmodulin-dependent protein kinase II expression. Abbreviations CaMKII, calmodulin-dependent protein kinase II; NMDA, N-methyl-D-aspartic acid; MAP-2, microtubule- associated 2; NSE, neuron-specific enolase; LDH, lactate dehydrogenase; PI, propidium iodide