title: Autophosphorylation as a possible mechanism of calcium/calmodulin-dependent protein kinase II inhibition during ischemia.
abstract: Cardiac arrest induced rat brain ischemia of 15 min duration produces a rapid and profound decrease in activity of calcium/calmodulin stimulated protein kinase (CaM-KII). In contrast to that, the total amount of enzyme protein remains stable as revealed by Western blotting (alpha subunit specific) analysis. Ischemic insult also results in translocation of the enzyme toward plasmatic membranes, reducing its content in soluble (cytosolic) fraction down to 7% with respect to 50% of control. The qualitatively similar translocation can be achieved by autophosphorylation of the control enzyme in vitro. Moreover, severely reduced response of immunoprecipitated enzyme to autophosphorylation observed after ischemia ex vivo probably reflects the higher level of its endogenous phosphorylation during the insult. The results strongly suggest that among various possible mechanisms of postischemic CaM-KII inhibition the most probable would be that involving abnormal or irreversible phosphorylation of the enzyme molecule. It would consequently block or inhibit the autophosphorylation/dephosphorylation cycle of endogenous CaM-KII interconversion necessary for its full catalytic activity.
authors.affiliation: Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, Warsaw.
authors.forename: T
authors.initials: T
authors.lastname: Zalewska
authors.forename: K
authors.initials: K
authors.lastname: Bialynicka-Birula
authors.forename: K
authors.initials: K
authors.lastname: Domańska-Janik
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology; D002545:Brain Ischemia / Q000201:enzymology* / Q000209:etiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D002384:Catalysis; D003600:Cytosol / Q000201:enzymology; D006323:Heart Arrest / Q000150:complications; D008297:Male; D008566:Membranes / Q000201:enzymology; D010766:Phosphorylation; D011233:Precipitin Tests; D051381:Rats; D017208:Rats, Wistar
chemical_list: D017871:Calcium-Calmodulin-Dependent Protein Kinases