A protein kinase C agonist, selective for the beta I isozyme, induces E-selectin and VCAM-1 expression on HUVEC but does not translocate PKC

Biochem Biophys Res Commun. 1993 Jun 30;193(3):1283-90. doi: 10.1006/bbrc.1993.1764.

Abstract

A protein kinase C (PKC) agonist selective for the beta I isozyme, 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA), induced NF-kappa B-like binding activity and surface expression of E-selectin and VCAM-1 in human umbilical vein endothelial cells (HUVEC), similar to the effects of tumor necrosis factor-alpha (TNF-alpha). Induction of E-selectin and VCAM-1 expression by dPPA was completely inhibited by the PKC inhibitors staurosporine and Ro31-7549. The PKC inhibitors also reduce TNF-alpha-induced VCAM-1 expression. However, neither dPPA nor TNF-alpha translocated PKC from the cytosolic to the plasma or nuclear membrane particulate fractions in HUVEC. These results indicate that activation of the beta I PKC isozyme is sufficient for expression of E-selectin and VCAM-1, and suggest that PKC may mediate the effects of TNF-alpha and dPPA without requiring the translocation normally associated with activation of PKC.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaloids / pharmacology
  • Base Sequence
  • Cell Adhesion Molecules / biosynthesis*
  • Cell Adhesion Molecules / genetics
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Cytosol / enzymology
  • E-Selectin
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Humans
  • Indoles / pharmacology
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism*
  • Kinetics
  • Maleimides / pharmacology
  • Membrane Glycoproteins / biosynthesis
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Oligonucleotide Probes
  • Phorbol Esters / pharmacology*
  • Promoter Regions, Genetic
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Staurosporine
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology
  • Umbilical Veins
  • Vascular Cell Adhesion Molecule-1

Substances

  • Alkaloids
  • Cell Adhesion Molecules
  • E-Selectin
  • Indoles
  • Isoenzymes
  • Maleimides
  • Membrane Glycoproteins
  • NF-kappa B
  • Oligonucleotide Probes
  • Phorbol Esters
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • 12-deoxyphorbolphenylacetate
  • thymeleatoxin
  • Protein Kinase C
  • Staurosporine
  • Tetradecanoylphorbol Acetate
  • Ro 31-7549