Isoform-specific membrane translocation of protein kinase C after ischemicpreconditioning

Mild cerebral anoxic/ischemic/stress insults promote 'tolerance' and thereb y protect the brain from subsequent 'lethal' anoxic/ischemic insults. We ex amined whether specific activation of PKC alpha, delta, epsilon, or xi isof orms is associated with ischemic preconditioning (IPC) in rat brain. IPC wa s produced by a 2-minute global cerebral ischemia. Membrane and cytosolic f ractions of the hippocampi were immunoblotted using specific antibodies for PKC alpha, delta, epsilon, and xi. PKC alpha showed a significant transloc ation to the membrane fraction from 30 min to 4 h and PKC delta at 4 h foll owing IPC. In contrast, the membrane/cytosol ratio of PKC epsilon showed a tendency to decrease at 30 min and 8 h, and the membrane/cytosol ratio of P KC was significantly decreased from 30 min to 24 h following IPC. These fin dings indicate PKC isoform-specific membrane translocations in the hippocam pus after brief global brain ischemia and suggest that activation of PKC al pha and PKC delta may be associated with IPC-induced tolerance in the rat h ippocampus.