Protein kinase Cdelta activation induces apoptosis in response to cardiac ischemia and reperfusion damage: a mechanism involving BAD and the mitochondria.

Abstract	Heart attacks caused by occlusion of coronary arteries are often treated by mechanical or enzymatic removal of the occlusion and reperfusion of the ischemic heart. It is now recognized that reperfusion per se contributes to myocardial damage, and there is a great interest in identifying the molecular basis of this damage. We recently showed that inhibiting protein kinase Cdelta (PKCdelta) protects the heart from ischemia and reperfusion-induced damage. Here, we demonstrate that PKCdelta activity and mitochondrial translocation at the onset of reperfusion mediates apoptosis by facilitating the accumulation and dephosphorylation of the pro-apoptotic BAD (Bcl-2-associated death promoter), dephosphorylation of Akt, cytochrome c release, PARP (poly(ADP-ribose) polymerase) cleavage, and DNA laddering. Our data suggest that PKCdelta activation has a critical proapoptotic role in cardiac responses following ischemia and reperfusion.
Authors	Christopher L Murriel, Eric Churchill, Koichi Inagaki, Luke I Szweda, Daria Mochly-Rosen
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 279 Issue 46 Pg. 47985-91 (Nov 12 2004) ISSN: 0021-9258 [Print] United States
PMID	15339931 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	BAD protein, human BCL2L1 protein, human Bad protein, rat Bcl2l1 protein, rat Carrier Proteins Protein Kinase Inhibitors Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 bcl-Associated Death Protein bcl-X Protein Cytochromes c PARP1 protein, human Parp1 protein, rat Poly (ADP-Ribose) Polymerase-1 Poly(ADP-ribose) Polymerases Prkcd protein, rat AKT1 protein, human Akt1 protein, rat Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt PRKCD protein, human Protein Kinase C Protein Kinase C-delta CASP3 protein, human Casp3 protein, rat Caspase 3 Caspases
Topics	Animals Apoptosis (physiology) Carrier Proteins (metabolism) Caspase 3 Caspases (metabolism) Cytochromes c (metabolism) Enzyme Activation Humans In Situ Nick-End Labeling In Vitro Techniques Male Mitochondria (metabolism) Myocardial Ischemia (metabolism) Myocardium (cytology, enzymology) Poly (ADP-Ribose) Polymerase-1 Poly(ADP-ribose) Polymerases Protein Kinase C (metabolism) Protein Kinase C-delta Protein Kinase Inhibitors (metabolism) Protein Serine-Threonine Kinases (metabolism) Proteins (metabolism) Proto-Oncogene Proteins (metabolism) Proto-Oncogene Proteins c-akt Proto-Oncogene Proteins c-bcl-2 (metabolism) Rats Rats, Wistar Reperfusion Injury (metabolism) Signal Transduction (physiology) bcl-Associated Death Protein bcl-X Protein

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