RT Journal Article
SR Electronic
T1 A specific inhibitor of calcium/calmodulin-dependent protein kinase-II provides neuroprotection against NMDA- and hypoxia/hypoglycemia-induced cell death
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4093
OP 4101
DO 10.1523/JNEUROSCI.15-05-04093.1995
VO 15
IS 5
A1 I Hajimohammadreza
A1 AW Probert
A1 LL Coughenour
A1 SA Borosky
A1 FW Marcoux
A1 PA Boxer
A1 KK Wang
YR 1995
UL http://www.jneurosci.org/content/15/5/4093.abstract
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.