Effect of PKC-zeta mediating Ang II-stimulated activation of CCDPK on rat cardiac fibroblast proliferation

Acta Pharmacol Sin. 2000 Feb;21(2):174-8.

Abstract

Aim: To investigate whether the effect of angiotensin (Ang) II or epidermal growth factor (EGF) on cardiac fibroblast proliferation involved in activation of extracellular signal-regulated kinase (ERK) 1/2 or Ca(2+)-calmodulin dependent protein kinase(CCDPK) mediated by protein kinase C (PKC)-zeta.

Methods: Relative activity of CCDPK was measured by Western blotting. DNA synthesis was assayed by [3H]thymidine incorporation.

Results: PDBU caused no decrease in Ang II- and 10% FCS-stimulated CCDPK activity and DNA synthesis. In contrary, 65% or 75% EGF- or tetradecanoylphorbol acetate (TDPA, formally called PMA)--stimulated CCDPK activity and 38% or 42% [3H]thymidine incorporation treated by PDBU were inhibited, respectively. Meanwhile 70% and 72% CCDPK activities induced by Ang II and EGF were inhibited by PD 98059, respectively.

Conclusion: PKC-zeta mediated Ang II-induced activation of CCDPK and cardiac fibroblast proliferation.

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Animals, Newborn
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Division / drug effects
  • Cells, Cultured
  • Epidermal Growth Factor / pharmacology
  • Fibroblasts / cytology
  • Flavonoids / pharmacology
  • Isoenzymes / metabolism
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Myocardium / cytology*
  • Protein Kinase C / metabolism*
  • Rats
  • Tetradecanoylphorbol Acetate

Substances

  • Flavonoids
  • Isoenzymes
  • Angiotensin II
  • Epidermal Growth Factor
  • protein kinase C zeta
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • Tetradecanoylphorbol Acetate
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one