A specific inhibitor of calcium/calmodulin-dependent protein kinase-II provides neuroprotection against NMDA- and hypoxia/hypoglycemia-induced cell death
| Autor: | Albert W. Probert, Peter A. Boxer, SA Borosky, Kevin K.W. Wang, Linda L. Coughenour, Iradj Hajimohammadreza, Frank W. Marcoux |
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| Rok vydání: | 1995 |
| Předmět: |
N-Methylaspartate
Cell Survival Carbazoles chemistry.chemical_element Kainate receptor AMPA receptor Naphthalenes Biology Calcium Pharmacology Hypoglycemia Neuroprotection Piperazines Indole Alkaloids Rats Sprague-Dawley Fetus 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine medicine Animals Polycyclic Compounds Enzyme Inhibitors Protein Kinase Inhibitors Cells Cultured Protein Kinase C Cerebral Cortex Neurons Cell Death Dose-Response Relationship Drug General Neuroscience Imidazoles Glutamate receptor Spectrin Long-term potentiation Articles Isoquinolines medicine.disease Genistein Isoflavones Cell Hypoxia Rats Kinetics chemistry Biochemistry Calcium-Calmodulin-Dependent Protein Kinases NMDA receptor |
| Zdroj: | The Journal of Neuroscience. 15:4093-4101 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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