Modulation of Activator Protein‐1 (AP‐1) Transcription Factor and Protein Kinase C by Hydrogen Peroxide and d‐α‐Tocopherol in Vascular Smooth Muscle Cells

Abstract

The effects of hydrogen peroxide, d‐α‐tocopherol and of d‐β‐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‐α‐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‐α‐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‐α‐Tocopherol promoted AP‐1 activation in quiescent cells but prevented its activation by phorbol myristate acetate. None of the described effects of d‐α‐tocopherol were shared by d‐β‐tocopherol, suggesting a non‐antioxidant mechanism as the basis of its action. The data show that hydrogen peroxide and d‐α‐tocopherol affect more than one element in the cell signal‐transduction cascade. Copyright © 1994, Wiley Blackwell. All rights reserved