Modulation of activator protein-1 (AP-1) transcription factor and protein kinase C by hydrogen peroxide and D-alpha-tocopherol in vascular smooth muscle cells

Eur J Biochem. 1994 Dec 1;226(2):393-402. doi: 10.1111/j.1432-1033.1994.tb20064.x.


The effects of hydrogen peroxide D-alpha-tocopherol and of D-beta-tocopherol on proliferation, protein kinase C and activator protein-1 (AP-1) activation have been studied in vascular smooth muscle cells. Cell proliferation, when activated by foetal calf serum, was inhibited by D-alpha-tocopherol. Protein kinase C activity was stimulated by hydrogen peroxide in a manner similar to phorbol myristate acetate; in the latter case, but not in the former, D-alpha-tocopherol inhibited the reaction. Hydrogen peroxide prevented phorbol-myristate-acetate-stimulated AP-1 binding to DNA but stimulated it if protein kinase C was down-regulated or inhibited. D-alpha-Tocopherol promoted AP-1 activation in quiescent cells but prevented its activation by phorbol myristate acetate. None of the described effects of D-alpha-tocopherol were shared by D-beta-tocopherol, suggesting a non-antioxidant mechanism as the basis of its action. The data show that hydrogen peroxide and D-alpha-tocopherol affect more than one element in the cell signal-transduction cascade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta
  • Base Sequence
  • Blotting, Northern
  • Cell Division / drug effects
  • Cell Line
  • Cells, Cultured
  • DNA / metabolism
  • Gene Expression
  • Genes, fos
  • Genes, jun
  • Hydrogen Peroxide / pharmacology*
  • Molecular Sequence Data
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Protein Kinase C / metabolism*
  • Rats
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription Factor AP-1 / metabolism*
  • Vitamin E / pharmacology*


  • Transcription Factor AP-1
  • Vitamin E
  • DNA
  • Hydrogen Peroxide
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate