배양 대뇌피질 신경세포에서 glutamate에 의한 Ca2+/calmodulin-dependent protein kiarse IV의 활성변화

Glutamate - induce d Modulation of Ca2+/Calmodulin-dependent Protein Kinase IV in Cultured Rat Cortical Neurons

The neuronal cell death induced by excess glutamate (Glu) has been implicated in many acute and chronic neurodegenerative diseases including cerebral ischemia. Glu-induced elevation of intra-cellular Ca2+ plays a critical role in the excitotoxicity partly through the activation of a variety of Ca2+-dependent enzymes. In the present study; we investigated the Glu-induced modulation of Ca2+/calmodulin-dependent protein kinase IV (CaMK IV, a multifunctional enzyme abundantly present in the nuclei of neurons. The exposure of cultured rat cortical neurons to 100μM Glu for 3 min dramatically increased CaMK IV activity up to 4.5-fold of the control-treated enzyme activity The activation was very rapid, reaching peak at 3 min and then declined gradually: Under the same experimental conditions, time-dependent acute and delayed neuronal cell death was observed. Immunoblot analyses using specific antibodies showed that the expressions of CaMK IV and CaMKαwere time-dependently modulated by Glu. Ttken together, These results imply that the modulation of CaMK IV activity by Glu may be involved in the cascade of events resulting in neuronal cell death in cortical cultures.