TY - JOUR
T1 - Glutamate‐Induced Loss of Ca2+/Calmodulin‐Dependent Protein Kinase II Activity in Cultured Rat Hippocampal Neurons
AU - Morioka, Motohiro
AU - Fukunaga, Kohji
AU - Nagahiro, Shinji
AU - Kurino, Masahito
AU - Ushio, Yukitaka
AU - Miyamoto, Eishichi
PY - 1995/5
Y1 - 1995/5
N2 - Abstract: The exposure of cultured rat hippocampal neurons to 500 µM glutamate for 20 min induced a 55% decrease in the total Ca2+/calmodulin‐dependent protein kinase II (CaM kinase II) activity. The Ca2+‐independent activity and autophosphorylation of CaM kinase II decreased to the same extent as the changes observed in total CaM kinase II activity, and these decreases in activities were prevented by pretreatment with MK‐801, an N‐methyl‐d‐aspartate (NMDA)‐type receptor antagonist, and the removal of extracellular calcium but not by antagonists against other types of glutamate receptors and protease inhibitors. Similarly, the decrease in the CaM kinase II activity was induced by a Ca2+ ionophore, ionomycin. Immunoblot analysis with the anti‐CaM kinase II antibody revealed a significant decrease in the amount of the enzyme in the soluble fraction, in contrast with the inverse increase in the insoluble fraction; thus, the translocation was probably induced during treatment of the cells with glutamate. These results suggest that glutamate released during brain ischemia induces a loss of CaM kinase II activity in hippocampal neurons, by stimulation of the NMDA receptor, and that inactivation of the enzyme may possibly be involved in the cascade of the glutamate neurotoxicity following brain ischemia.
AB - Abstract: The exposure of cultured rat hippocampal neurons to 500 µM glutamate for 20 min induced a 55% decrease in the total Ca2+/calmodulin‐dependent protein kinase II (CaM kinase II) activity. The Ca2+‐independent activity and autophosphorylation of CaM kinase II decreased to the same extent as the changes observed in total CaM kinase II activity, and these decreases in activities were prevented by pretreatment with MK‐801, an N‐methyl‐d‐aspartate (NMDA)‐type receptor antagonist, and the removal of extracellular calcium but not by antagonists against other types of glutamate receptors and protease inhibitors. Similarly, the decrease in the CaM kinase II activity was induced by a Ca2+ ionophore, ionomycin. Immunoblot analysis with the anti‐CaM kinase II antibody revealed a significant decrease in the amount of the enzyme in the soluble fraction, in contrast with the inverse increase in the insoluble fraction; thus, the translocation was probably induced during treatment of the cells with glutamate. These results suggest that glutamate released during brain ischemia induces a loss of CaM kinase II activity in hippocampal neurons, by stimulation of the NMDA receptor, and that inactivation of the enzyme may possibly be involved in the cascade of the glutamate neurotoxicity following brain ischemia.
KW - Brain ischemia
KW - Ca/calmodulin‐dependent protein kinase II
KW - Glutamate neurotoxicity
KW - Hippocampus
KW - NMDA receptor
UR - http://www.scopus.com/inward/record.url?scp=0028986070&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028986070&partnerID=8YFLogxK
U2 - 10.1046/j.1471-4159.1995.64052132.x
DO - 10.1046/j.1471-4159.1995.64052132.x
M3 - Article
C2 - 7722497
AN - SCOPUS:0028986070
VL - 64
SP - 2132
EP - 2139
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 5
ER -