PKC translocation without changes in G alpha(q) and PLC-beta protein abundance in cardiac hypertrophy and failure

Activation of protein kinase C (PKC) has been implicated as playing a Bey r ole in the pathogenesis of cardiac hypertrophy This study investigates the response of several signal transduction proteins responsible for PKC activa tion during the transition from compensated pressure-overload hypertrophy ( POH) to congestive heart failure (CHF). Pressure overload was produced on m ale, adult, Hartley strain guinea pigs using a ligature around the descendi ng thoracic aorta. Sham-operated controls, POH, and CHF groups were identif ied based on left ventricular hypertrophy, pulmonary congestion, and isolat ed heart Langendorff mechanics. Quantitative immunoblotting revealed phosph olipase C (PLC)-beta I and G alpha(q) were unchanged during POH and CHF, as were RGS2, RGS3, and RGS4 (regulators of G protein signaling, which are ac tivators of intrinsic GTPase activity). Translocation of PKC-alpha, -epsilo n, and -gamma from cytosolic to membranous fractions were significantly inc reased during POH and CHF. Cytosolic PKC activity was also elevated during POH. We conclude that differential PKC activation may be mediated by increa ses in G alpha(q) and PLC-beta I activity rather than upregulation of expre ssion.