Does protein kinase C play a pivotal role in the mechanisms of ischemic preconditioning?
This communication reviews the evidence for the pivotal role of protein kinase C in ischemic myocardial preconditioning. It is believed that several intracellular signalling pathways via receptor-coupled phospholipase C and its "cross-talk" with phospholipase D converge to activation of protein kinase C isotypes which is followed by phosphorylation of until now (a number of) unknown target proteins which produce the protective state of ischemic preconditioning. After briefly introducing the general biochemical properties of protein kinase C, its isotypes and the limitations of the methodology used to investigate the role of protein kinase C, studies are discussed in which pharmacological inhibition and activation and (immunore) activity and/or isotypes measurements 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 stability (of covalently bound phosphate) of phosphorylated substrate proteins.
Gho
B C
BC
Department of Biochemistry (Cardiovascular Research Institute COEUR), Erasmus University Rotterdam, The Netherlands.
Eskildsen-Helmond
Y E
YE
de Zeeuw
S
S
Lamers
J M
JM
Verdouw
P D
PD
D000818:Animals; D004789:Enzyme Activation; D019157:Ischemic Preconditioning, Myocardial; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology; D010739:Phospholipase D / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism
D007527:Isoenzymes; D011493:Protein Kinase C; D010738:Type C Phospholipases; D010739:Phospholipase D