A. Azzi et al., ALPHA-TOCOPHEROL AS A MODULATOR OF SMOOTH-MUSCLE CELL-PROLIFERATION, Prostaglandins, leukotrienes and essential fatty acids, 57(4-5), 1997, pp. 507-514
The effects of alpha-tocopherol and beta-tocopherol have been studied
in rat and human aortic smooth muscle cells. alpha-tocopherol, but not
beta-tocopherol, inhibited smooth muscle cell proliferation and prote
in kinase C in a dose-dependent manner, at concentrations ranging from
10 to 50 mu M. beta-tocopherol added simultaneously with alpha-tocoph
erol prevented both proliferation and protein kinase C inhibition. Pro
tein kinase C inhibition was cell cycle-dependent and it was prevented
by okadaic acid, a protein phosphatase inhibitor. Protein kinase C ac
tivity measured from aortas of cholesterol-fed rabbits was also inhibi
ted by alpha-tocopherol. By using protein kinase C (PKC) isoform-speci
fic inhibitors and immunoprecipitation reactions it was found that PKC
-alpha was selectively inhibited by alpha-tocopherol. Further, an acti
vation of protein phosphatase 2A by alpha-tocopherol was found, which
caused PKC-alpha dephosphorylation and inhibition. Ultimately, this ca
scade of events at the level of cell signal transduction leads to the
inhibition of smooth muscle cell proliferation.