TY - JOUR
T1 - Protein kinase Cδ activation induces apoptosis in response to cardiac ischemia and reperfusion damage
T2 - A mechanism involving bad and the mitochondria
AU - Murriel, Christopher L.
AU - Churchill, Eric
AU - Inagaki, Koichi
AU - Szweda, Luke I.
AU - Mochly-Rosen, Daria
PY - 2004/11/12
Y1 - 2004/11/12
N2 - 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 Cδ (PKCδ) protects the heart from ischemia and reperfusion-induced damage. Here, we demonstrate that PKCδ 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 PKCδ activation has a critical pro-apoptotic role in cardiac responses following ischemia and reperfusion.
AB - 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 Cδ (PKCδ) protects the heart from ischemia and reperfusion-induced damage. Here, we demonstrate that PKCδ 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 PKCδ activation has a critical pro-apoptotic role in cardiac responses following ischemia and reperfusion.
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U2 - 10.1074/jbc.M405071200
DO - 10.1074/jbc.M405071200
M3 - Article
C2 - 15339931
AN - SCOPUS:9144256765
SN - 0021-9258
VL - 279
SP - 47985
EP - 47991
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 46
ER -