The roles of PKCdelta and epsilon isoenzymes in the regulation of myocardial ischaemia/reperfusion injury.
Reperfusion of ischaemic cardiac tissue is associated with increased apoptosis and oncosis, resulting in diminished heart function. Short bouts of ischaemia before the prolonged ischaemic event (ischaemic preconditioning) protect the heart from injury mediated by reperfusion. The PKC (protein kinase C) family of serine/threonine kinases are involved in many different signalling processes. Two calcium-insensitive isoforms of the novel PKC subfamily, PKCdelta and epsilon, play opposing roles in ischaemia/reperfusion injury. Activation of PKCdelta during reperfusion induces cell death through the regulation of mitochondrial function and induction of apoptosis and oncosis. In contrast, activation of PKCepsilon before ischaemia protects mitochondrial function and diminishes apoptosis and oncosis. How can two highly homologous PKC isoenzymes play such opposing roles through the regulation of mitochondrial function? This review will highlight what is known about PKCdelta and epsilon function during ischaemia/reperfusion injury and will suggest a novel regulatory pathway which determines the fate of the cell following ischaemic stress.
Churchill
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Department of Chemical and Systems Biology, Stanford University School of Medicine, CCSR, Rm 3145A, 269 Campus Drive, Stanford, CA 94305-5174, U.S.A.
Mochly-Rosen
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D006868:Hydrolysis; D007527:Isoenzymes / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000378:metabolism*
D007527:Isoenzymes; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D046988:Proteasome Endopeptidase Complex