KN-62 provides neuroprotection against glutamate-induced excitotoxicity in neurons.
OBJECTIVE
To study the effects of KN-62, an inhibitor of Ca(2+)-calmodulin dependent protein kinase II (CCDPK II), on the damage of cortical neurons and mechanisms of the loss of CCDPK II activity induced by sodium glutamate (Glu).


METHODS
CCDPK II activity was measured by 32P incorporation and backphosphorylations of endogenous proteins were studied by autoradiography.


RESULTS
1) KN-62 provided partial protection against excitotoxical damage only before Glu (100 mumol.L-1, 10 min) treatment. 2) KN-62 markedly suppressed the loss of CCDPK II activity induced by Glu from 48.0% to 90.6%. 3) Backphosphorylation of endogenous proteins (especially the 50 kDa protein) reduced to 78.2% of control after treatment with Glu, and the reduction was protected with KN-62 added before Glu.


CONCLUSIONS
KN-62 provided the protection against excitotoxicity and the loss of CCDPK II activity as well as backphosphorylation of endogenous proteins induced by Glu. The neuroprotection provided by KN-62 was due to the inhibition of autophosphorylation of CCDPK II.
Gao
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Research Center of Biochemistry and Molecular Biology, Xuzhou Medical College, Xuzhou 221002, China.
Zhang
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GY
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D005260:Female; D018698:Glutamic Acid / Q000633:toxicity; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D018698:Glutamic Acid; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017871:Calcium-Calmodulin-Dependent Protein Kinases