D-ALPHA-TOCOPHEROL INHIBITION OF VASCULAR SMOOTH-MUSCLE CELL-PROLIFERATION OCCURS AT PHYSIOLOGICAL CONCENTRATIONS, CORRELATES WITH PROTEIN-KINASE-C INHIBITION, AND IS INDEPENDENT OF ITS ANTIOXIDANT PROPERTIES

d-alpha-Tocopherol, but not d-beta-tocopherol, negatively regulates pr oliferation of vascular smooth muscle cells at physiological concentra tions, d-alpha-Tocopherol inhibits protein kinase C (PKC) activity, wh ereas d-beta-tocopherol is ineffective, Furthermore d-beta-tocopherol prevents the inhibition of cell growth and of PKC activity caused by d -alpha-tocopherol, The negative regulation by d-alpha-tocopherol of PI ;C activity appears to be the cause and not the effect of smooth muscl e cell growth inhibition, d-alpha-Tocopherol does not act by binding t o PKC directly but presumably by preventing PKC activation, It is conc luded that, in vascular smooth muscle cells, d-alpha-tocopherol acts s pecifically through a nonantioxidant mechanism and exerts a negative c ontrol on a signal transduction path,cay regulating cell proliferation .