Preservation of Base-line Hemodynamic Function and Loss of Inducible Cardioprotection in Adult Mice Lacking Protein Kinase Cϵ
Journal of Biological Chemistry
Signaling pathways involving protein kinase C isozymes are modulators of cardiovascular development and response to injury. Protein kinase C⑀ activation in cardiac myocytes reduces necrosis caused by coronary artery disease. However, it is unclear whether protein kinase C⑀ function is required for normal cardiac development or inducible protection against oxidative stress. Protein kinase C␦ activation is also observed during cardiac preconditioning. However, its role as a promoter or inhibitor
... moter or inhibitor of injury is controversial. We examined hearts from protein kinase C⑀ knock-out mice under physiological conditions and during acute ischemia reperfusion. Null-mutant and wild-type mice displayed equivalent base-line morphology and hemodynamic function. Targeted disruption of the protein kinase C⑀ gene blocked cardioprotection caused by ischemic preconditioning and ␣ 1 -adrenergic receptor stimulation. Protein kinase C␦ activation increased in protein kinase C⑀ knock-out myocytes without altering resistance to injury. These observations support protein kinase C⑀ activation as an essential component of cardioprotective signaling. Our results favor protein kinase C␦ activation as a mediator of normal growth. This study advances the understanding of cellular mechanisms responsible for preservation of myocardial integrity as potential targets for prevention and treatment of ischemic heart disease.