PT  - JOURNAL ARTICLE
AU  - I Hajimohammadreza
AU  - AW Probert
AU  - LL Coughenour
AU  - SA Borosky
AU  - FW Marcoux
AU  - PA Boxer
AU  - KK Wang
TI  - A specific inhibitor of calcium/calmodulin-dependent protein kinase-II provides neuroprotection against NMDA- and hypoxia/hypoglycemia-induced cell death
AID  - 10.1523/JNEUROSCI.15-05-04093.1995
DP  - 1995 May 01
TA  - The Journal of Neuroscience
PG  - 4093--4101
VI  - 15
IP  - 5
4099  - http://www.jneurosci.org/content/15/5/4093.short
4100  - http://www.jneurosci.org/content/15/5/4093.full
SO  - J. Neurosci.1995 May 01; 15
AB  - Calcium/calmodulin-dependent protein kinase-II (CamK-II) is a major neuronal protein which plays a significant role in the cellular process of long-term potentiation (LTP), and vesicular release of neurotransmitters. Here, we show that KN-62, 1-[N,O-bis(5- isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4- phenylpiperazine, a specific cell-permeable inhibitor of CamK-II substantially protected neurons from (1) acute NMDA toxicity and (2) hypoxia/hypoglycemia- induced neuronal injury in fetal rat cortical cultures. KN-62 did not directly inhibit glutamate, kainate, alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionate (AMPA), glycine, or [piperidyl-3,4-(N)]-(N-[1-(2- thienyl)cyclohexyl]-3,4-piperidine) (TCP) binding to rat brain membranes. Finally, KN-62 significantly reduced cellular calcium accumulation following either NMDA challenge or hypoxia/hypoglycemia insult. Our results show that CamK-II plays a key role in mediating some of the biochemical events leading to cell death following an acute excitotoxic insult.