title: Characterization of MAP kinase and PKC isoform and effect of ACE inhibition in hypertrophy in vivo.
abstract: Protein kinase C (PKC) and mitogen-activated protein (MAP) kinase activation appear important in conferring hypertrophy in vitro. However, the response of PKC and MAP kinase to stimuli known to induce hypertrophy in vivo has not been determined. We recently demonstrated that pressure-overload hypertrophy induced a transiently transfected gene driven by an hypertrophy responsive enhancer (HRE) through a marked increase in binding activity of its interacting nuclear factor (HRF). These data suggested that the HRE/HRF could serve as a target for evaluating the signal transduction events responsible for hypertrophy in vivo. Accordingly, we characterized MAP kinase and PKC isoform activation, injected HRE driven reporter gene expression, and HRF binding activity in rat hearts subjected to ascending aortic clipping or sham operation in the presence of the angiotensin-converting enzyme (ACE) inhibitor fosinopril, hydralazine, or no treatment. Analyses showed that PKC-epsilon and MAP kinase were acutely activated following ascending aortic ligature and that fosinopril significantly inhibited but did not completely abrogate PKC-epsilon and MAP kinase activation. However, fosinopril completely prevented pressure overload-mediated induction of HRE containing constructs and obviated increased HRF binding activity. These results suggest a direct relationship between ACE activity and HRE/HRF-mediated gene activation and imply that PKC-epsilon and MAP kinase may be involved in transducing this signal.
authors.affiliation: Division of Cardiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0542, USA.
authors.forename: L
authors.initials: L
authors.lastname: Kim
authors.forename: T
authors.initials: T
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Fu
authors.forename: M E
authors.initials: ME
authors.lastname: Ritchie
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D006332:Cardiomegaly / Q000201:enzymology* / Q000209:etiology; D004789:Enzyme Activation / Q000187:drug effects; D017328:Fosinopril / Q000494:pharmacology; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000150:complications; D007527:Isoenzymes / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020218:Response Elements / Q000235:genetics; D014162:Transfection
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007527:Isoenzymes; D009687:Nuclear Proteins; D010750:Phosphoproteins; D006830:Hydralazine; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D017328:Fosinopril