Activation and inhibition of protein kinase C protect rat neuronal cultures against ischemia-reperfusion insult

The effect of activation and inhibition of protein kinase C (PKC) on the capacity of neurons to resist subsequent ischemic and ischemia-reperfusion- induced cell injury, was studied in a model of primary rat neuronal cultures, subjected to chemical ischemia. Activation of PKC by 1,2 dioctanoyl-rac- glycerol (DOG; 1 μM), or phorbol 12-myristate 13-acetate (PMA; 1 μM), as well as inhibition of the enzyme bY chelerythrine (10 μM), or by calphostin C (0.2 μM), 10 min before the ischemic insult, resulted in acquisition of resistance against the two insults. The length of the 'time window of protection' induced by exposure to DOG and to chelerythrine was studied and found to last for several days. The results demonstrate an apparently 'paradoxical' phenomenon in which both activation and inhibition of PKC in the same tissue induce protection. This may be explained by differential activation of various PKC isoforms.