Protein Kinase C Signaling and Expression of the Diabetic Cardiac Phenotype

摘要

Summary. The focus of this review will be recent advances in the molecular biology of protein kinase C (PKC) signaling in cardiac myocytes and the application of these novel techniques to study the pathobiology of diabetic cardiac myopathy. The PKC family of serine/threonine kinases have been implicated in a diverse array of biologic responses in health and disease. Compelling evidence has linked PKC signaling to hyperglycemia mediated ceil injury. Although the cardiac myocyte has not been traditionally considered a major target cell for insulin, high ambient concentration of glucose promotes the activation of cardiac PKC isozymes, that target physiologically relevant intracellular substrates. The availability of genetically engineered mice, with targeted activation of distinct PKC isozyme (PKCe) in cardiac muscle cells and the development of selective peptide PKC modulators, provides an approach to examine PKC signaling events in the diabetic heart, and to explore the in vivo and in vitro consequences of this signaling cascade. The rapid growth of knowledge in this area Is critical to the development of therapeutic strategies with the potential to arrest or reverse the progression of diabetic cardiomyopathy.