DOES PROTEIN-KINASE-C PLAY A PIVOTAL ROLE IN THE MECHANISMS OF ISCHEMIC PRECONDITIONING

This communication reviews the evidence for the pivotal role of protei n kinase C in ischemic myocardial preconditioning. It is believed that several intracellular signalling pathways via receptor-coupled phosph olipase C and its ''cross-talk'' with phospholipase D converge to acti vation of protein kinase C isotypes which is followed by phosphorylati on of until now (a number of) unknown target proteins which produce th e protective state of ischemic preconditioning. After briefly introduc ing the general biochemical properties of protein kinase C, its isotyp es and the limitations of the methodology used to investigate the role of protein kinase C, studies are discussed in which pharmacological i nhibition and activation and (immunore)activity and/or isotypes measur ements of protein kinase C isotypes were applied to assess the role of activation of protein kinase C in ischemic myocardial preconditioning . It is concluded that definitive proof for the involvement of protein kinase C in preconditioning requires future studies which must focus on the isotype(s) of protein kinase C that are activated, the duration of action, cellular translocation sites and the identity and stabilit y (of covalently bound phosphate) of phosphorylated substrate proteins .