title: PKC translocation without changes in Galphaq and PLC-beta protein abundance in cardiac hypertrophy and failure.
abstract: Activation of protein kinase C (PKC) has been implicated as playing a key role in the pathogenesis of cardiac hypertrophy. This study investigates the response of several signal transduction proteins responsible for PKC activation during the transition from compensated pressure-overload hypertrophy (POH) to congestive heart failure (CHF). Pressure overload was produced on male, adult, Hartley strain guinea pigs using a ligature around the descending thoracic aorta. Sham-operated controls, POH, and CHF groups were identified based on left ventricular hypertrophy, pulmonary congestion, and isolated heart Langendorff mechanics. Quantitative immunoblotting revealed phospholipase C (PLC)-betaI and Galphaq were unchanged during POH and CHF, as were RGS2, RGS3, and RGS4 (regulators of G protein signaling, which are activators of intrinsic GTPase activity). Translocation of PKC-alpha, -epsilon, and -gamma from cytosolic to membranous fractions were significantly increased during POH and CHF. Cytosolic PKC activity was also elevated during POH. We conclude that differential PKC activation may be mediated by increases in Galphaq and PLC-betaI activity rather than upregulation of expression.
authors.affiliation: Department of Medicine, Case Western Reserve University, University Hospital of Cleveland, Cleveland, Ohio 44106-5029, USA.
authors.forename: T
authors.initials: T
authors.lastname: Jalili
authors.forename: Y
authors.initials: Y
authors.lastname: Takeishi
authors.forename: G
authors.initials: G
authors.lastname: Song
authors.forename: N A
authors.initials: NA
authors.lastname: Ball
authors.forename: G
authors.initials: G
authors.lastname: Howles
authors.forename: R A
authors.initials: RA
authors.lastname: Walsh
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D006168:Guinea Pigs; D006333:Heart Failure / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D054799:Phospholipase C beta; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D020710:RGS Proteins / Q000378:metabolism; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; D007527:Isoenzymes; D020710:RGS Proteins; C105345:Rgs2 protein, mouse; C415085:Rgs3 protein, mouse; C098799:RGS4 protein; C087857:protein kinase C gamma; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D019204:GTP-Binding Proteins; D043802:GTP-Binding Protein alpha Subunits, Gq-G11