Ischemia-induced loss of brain calcium/calmodulin-dependent protein kinase II.
Forebrain ischemia in gerbils, produced by brief bilateral carotid occlusion, induced the dramatic loss of Ca2+/calmodulin-dependent protein kinase II (CaM-kinase II) as determined by both kinase activity assays and western blot analysis. In cortex and hippocampus, cytosolic CaM-kinase II was completely lost within 2-5 min of ischemia. Particulate CaM-kinase II was more stable and decreased in level approximately 40% after 10 min of ischemia followed by 2 h of reperfusion. CaM-kinase II in cerebellum, which does not become ischemic, was not affected. The rapid loss of CaM-kinase II within 2-5 min was quite specific because cytosolic cyclic AMP kinase and protein kinase C in hippocampus were not affected. These data indicate that cytosolic CaM-kinase II is one of the most rapidly degraded proteins after brief ischemia. Because the multifunctional CaM-kinase II has been implicated in the regulation of numerous neuronal functions, its loss may destine the neuronal cell for death.
Yamamoto
H
H
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee.
Fukunaga
K
K
Lee
K
K
Soderling
T R
TR
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002545:Brain Ischemia / Q000201:enzymology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002540:Cerebral Cortex / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D005849:Gerbillinae; D006624:Hippocampus / Q000201:enzymology; D015151:Immunoblotting; D011494:Protein Kinases / Q000378:metabolism*; D013997:Time Factors
D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases