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This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/H1862    most recent 01346.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Kong, L. Articles by Yan, S.-F. Search for Related Content PubMed PubMed Citation Articles by Kong, L. Articles by Yan, S.-F.

PKCβ modulates ischemia-reperfusion injury in the heart

Departments of ¹Surgery, ²Pathology, and ³Medicine, College of Physicians and Surgeons, Columbia University, New York, New York; and ⁴Department of Nephrology, Hannover Medical School, Hannover, Germany

Submitted 16 November 2007 ; accepted in final form 28 January 2008

Protein kinase C-βII (PKCβII) is an important modulator of cellular stress responses. To test the hypothesis that PKCβII modulates the response to myocardial ischemia-reperfusion (I/R) injury, we subjected mice to occlusion and reperfusion of the left anterior descending coronary artery. Homozygous PKCβ-null (PKCβ^–/–) and wild-type mice fed the PKCβ inhibitor ruboxistaurin displayed significantly decreased infarct size and enhanced recovery of left ventricular (LV) function and reduced markers of cellular necrosis and serum creatine phosphokinase and lactate dehydrogenase levels compared with wild-type or vehicle-treated animals after 30 min of ischemia followed by 48 h of reperfusion. Our studies revealed that membrane translocation of PKCβII in LV tissue was sustained after I/R and that gene deletion or pharmacological blockade of PKCβ protected ischemic myocardium. Homozygous deletion of PKCβ significantly diminished phosphorylation of c-Jun NH₂-terminal mitogen-activated protein kinase and expression of activated caspase-3 in LV tissue of mice subjected to I/R. These data implicate PKCβ in I/R-mediated myocardial injury, at least in part via phosphorylation of JNK, and suggest that blockade of PKCβ may represent a potent strategy to protect the vulnerable myocardium.

myocardial ischemia; JNK; caspase-3

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