Alpha-tocopherol as a modulator of smooth muscle cell proliferation.
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 protein kinase C in a dose-dependent manner, at concentrations ranging from 10 to 50 microM. Beta-tocopherol added simultaneously with alpha-tocopherol prevented both proliferation ... and protein kinase C inhibition. Protein kinase C inhibition was cell cycle-dependent and it was prevented by okadaic acid, a protein phosphatase inhibitor. Protein kinase C activity measured from aortas of cholesterol-fed rabbits was also inhibited by alpha-tocopherol. By using protein kinase C (PKC) isoform-specific inhibitors and immunoprecipitation reactions it was found that PKC-alpha was selectively inhibited by alpha-tocopherol. Further, an activation of protein phosphatase 2A by alpha-tocopherol was found, which caused PKC-alpha dephosphorylation and inhibition. Ultimately, this cascade of events at the level of cell signal transduction leads to the inhibition of smooth muscle cell proliferation.
Mesh Terms:
Animals, Binding Sites, Cell Cycle, Cell Division, Humans, Isoenzymes, Male, Muscle, Smooth, Vascular, Phosphoprotein Phosphatases, Protein Kinase C, Protein Kinase C-alpha, Protein Phosphatase 2, Rabbits, Rats, Vitamin E
Animals, Binding Sites, Cell Cycle, Cell Division, Humans, Isoenzymes, Male, Muscle, Smooth, Vascular, Phosphoprotein Phosphatases, Protein Kinase C, Protein Kinase C-alpha, Protein Phosphatase 2, Rabbits, Rats, Vitamin E
Prostaglandins Leukot. Essent. Fatty Acids
Date: Oct. 01, 1997
PubMed ID: 9430404
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