Depolarization induces NR2A tyrosine phosphorylation and neuronal apoptosis.
Can J Neurol Sci
; 38(6): 880-6, 2011 Nov.
Article
en En
| MEDLINE
| ID: mdl-22030427
ABSTRACT
BACKGROUND:
Cytosol Ca2+ overload plays a vital role in ischemic neuronal damage, which is largely contributed by the Ca2+ influx through L-type voltage-gated calcium channels (L-VGCCs) and N-methyl-D-aspartate (NMDA) type glutamate receptors. In this article, L-VGCCs were activated by depolarization to investigate the cross-talk between NMDA receptors and L-VGCCs.METHODS:
Depolarization was induced by 20 minutes incubation of 75 mM KCl in cultured rat cortical neuron. Apoptosis-like neuronal death was detected by DAPI staining. Tyrosine phosphorylation of NMDA receptor subunit 2A (NR2A), interactions of Src and NR2A were detected by immunoblot and immunoprecipitation.RESULTS:
Depolarization induced cortical neuron apoptosis-like cell death after 24 hours of restoration. The apoptosis was partially inhibited by 5 mM EGTA, 100 µM Cd2+, 10 µM nimodipine, 100 µM genistein, 20 µM MK-801, 2 µM PP2 and combined treatment of nimodipine and MK-801. NR2A tyrosine phosphorylation increased after depolarization, and the increase was inhibited by the drugs listed above. Moreover, non-receptor tyrosine kinase Src bound with NR2A after depolarization and restoration. The binding was also inhibited by the drugs listed above.CONCLUSIONS:
The results indicated that depolarization-induced neuronal death might be due to extracellular Ca2+ influx through L-VGCCs and subsequently Src activationmediated NR2A tyrosine phosphorylation.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tirosina
/
Corteza Cerebral
/
Apoptosis
/
Receptores de N-Metil-D-Aspartato
/
Neuronas
Límite:
Animals
Idioma:
En
Revista:
Can J Neurol Sci
Año:
2011
Tipo del documento:
Article
País de afiliación:
China