Protein Kinase Calpha Negatively Regulates Systolic and Diastolic Function in Pathological Hypertrophy

Details

• Personal Author:
  Bodi I ; Dorn GW 2nd ; Hahn HS ; Hilty KC ; Liggett SB ; Marreez Y ; Odley A ; Schwartz A ; Sterbling A ; Yussman MG
• Description:
  The protein kinase C (PKC) family is implicated in cardiac hypertrophy, contractile failure, and beta-adrenergic receptor (betaAR) dysfunction. Herein, we describe the effects of gain- and loss-of-PKCalpha function using transgenic expression of conventional PKC isoform translocation modifiers. In contrast to previously studied PKC isoforms, activation of PKCalpha failed to induce cardiac hypertrophy, but instead caused betaAR insensitivity and ventricular dysfunction. PKCalpha inhibition had opposite effects. Because PKCalpha is upregulated in human and experimental cardiac hypertrophy and failure, its effects were also assessed in the context of the Galphaq overexpression model (in which PKCalpha is transcriptionally upregulated). Normalization (inhibition) of PKCalpha activity in Galpha(q) hearts improved systolic and diastolic function, whereas further activation of PKCalpha caused a lethal restrictive cardiomyopathy with marked interstitial fibrosis. These results define pathological roles for PKCalpha as a negative regulator of ventricular systolic and diastolic function. [Description provided by NIOSH]
• Subjects:
  Animals Cardiovascular System Enzymes Fibrosis Genetics Laboratories Occupational Health Safety
• Keywords:
  Animal-studies Diseases Enzyme-inhibitors Enzymology Heart Heart-rate Laboratory-animals Models Peptides Pharmacology
• ISSN:
  0009-7330
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  93
• Issue:
  11
• NIOSHTIC Number:
  nn:20029175
• Citation:
  Circ Res 2003 Nov; 93(11):1111-1119
• Contact Point Address:
  G.W. Dorn II, Department of Internal Medicine, University of Cincinnati Medical Center, 231 Albert B. Sabin Way, Cincinnati, Ohio 45267-0542, USA
• Email:
  dorngw@ucmail.uc.edu
• Federal Fiscal Year:
  2004
• Peer Reviewed:
  True
• Source Full Name:
  Circulation Research
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a6d859561df7cbd5c5fd32e9112d6957b6d441427a49e87622cd173093534b295b15f19411cd43e470018b2239e91126b76d50e6a948a0e6ec74915f964d1b47
• Download URL:
  https://stacks.cdc.gov/view/cdc/190219/cdc_190219_DS1.pdf
• File Type:
  [PDF - 400.16 KB ]