CASEIN KINASE-II ACTIVITY IN THE POSTISCHEMIC RAT-BRAIN INCREASES IN BRAIN-REGIONS RESISTANT TO ISCHEMIA AND DECREASES IN VULNERABLE AREAS

Casein kinase II (CKII) is a protein kinase acting in the intracellula r cascade of reactions activated by growth factor receptors, and that has a profound influence on cell proliferation and survival. In this i nvestigation, we studied the changes in the activity and levels of CKI I in the rat brain exposed to 10, 15 and 20 min of transient forebrain ischemia followed by variable periods of reperfusion. The cytosolic C KII activity decreased during reperfusion by approximately 30 and appr oximately 50% in the selectively vulnerable areas, striatum and the CA 1 region of the hippocampus, respectively. In the resistant CA3 region of hippocampus and neocortex, the activity increased by approximately 20 and approximately 60%, respectively. The postischemic changes in C KII activity were dependent on the duration of the ischemic insult. Th e levels of CKII did not change after ischemia, suggesting that the en zyme is modulated by covalent modification or is interacting with an e ndogenous inhibitor/activator. Treatment of the cytosolic fraction fro m cortex of rats exposed to ischemia and 1 h of reperfusion with agaro se-bound phosphatase decreased the activity of CKII to control levels, suggesting that CKII activation after ischemia involves a phosphoryla tion of the enzyme. The correlation between postischemic CKII activity and neuronal survival implies that preservation or activation of CKII activity may be important for neuronal survival after cerebral ischem ia.