Brief ischemic episode, which in itself is not lethal, confers tolerance to subsequent ischemic insults. Since intracellular signal transduction system has been implicated in ischemic cell death, we studied the effect of pre-conditioning on the changes in the subcellular distribution of
protein kinase Cgamma (PKCgamma) as well as
CaM kinase II (
CaMKII). Gerbils were pre-conditioned by a sublethal 2 min
cerebral ischemia 24 h prior to lethal 5 min
ischemia. The pre-conditioning generally downregulated PKCgamma and
CaMKII in the CA1 hippocampus. Especially at the starting point of the second lethal
ischemia, the cytosolic PKCgamma level was about 40% lower in the pre-conditioned group. Also, the crude synaptosomal
CaMKII level at 24 h reperfusion following the second
ischemia was significantly lower in the pre-conditioned group, showing enhanced recovery of
CaMKII translocation. Present results suggest that ischemic pre-conditioning may downregulate
calcium-mediated cell signaling system, enhancing normalization of
calcium homeostasis, perturbed by the second
ischemia of lethal duration.