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 t he capacity of neurons to resist subsequent ischemic and ischemia-repe rfusion-induced cell injury, was studied in a model of primary rat neu ronal cultures, subjected to chemical ischemia. Activation of PKC by 1 ,2 dioctanoyl-rac-glycerol (DOG; 1 mu M), or phorbol 12-myristate 13-a cetate (PMA; I mu M), as well as inhibition of the enzyme by cheleryth rine (10 mu M), or by calphostin C (0.2 mu M), 10 min before the ische mic insult, resulted in acquisition of resistance against the two insu lts. 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 ind uce protection. This may be explained by differential activation of va rious PKC isoforms. (C) 1997 Elsevier Science Ireland Ltd.