Rat and human vascular smooth muscle cell proliferation is specifically sensitive to alpha-tocopherol, but not beta-tocopherol. The former, but not the latter, is capable of limiting proliferation and inhibiting protein kinase C activity in a dose-dependent manner. The phenomenon occurs at concentrations in the range 10-50 microM. beta-tocopherol addition together with alpha-tocopherol, prevents both cell growth and protein kinase C inhibition. alpha-tocopherol increases de novo synthesis of protein kinase C molecules. The enzyme specific activity, however, is diminished, due to a decreased phosphorylation of protein kinase C, occurring in the presence of alpha-tocopherol. Experiments with protein kinase C isoform-specific inhibitors and precipitating antibodies show that the only isoform affected by alpha-tocopherol is protein kinase C-alpha. The effect of alpha-tocopherol is prevented by okadaic acid indicating a phosphatase of the PP2A type as responsible for protein kinase C-alpha dephosphorylation produced in the presence of alpha-tocopherol. At a gene level alpha-tocopherol but not beta-tocopherol induces a transient activation of alpha-tropomyosin gene transcription and protein expression. It is proposed that, by inhibiting protein kinase C activity via an activation of a phosphatase PP2A, alpha-tocopherol controls smooth muscle cell proliferation through changes in gene expression.
The effect of K K-tocopherol (vitamin E) on gene expression in rat vascular smooth muscle cells was studied by the differential display technique. One gene out of about 1000 genes analyzed, identified as K K-tropomyosin, showed an increased transcription level caused by K K-tocopherol treatment. Northern and Western blot analysis revealed a time-dependent transient up-regulation of the amount of mRNA (peak between 2 and 3 h) and protein (peak at 5 h) in K K-tocopherol-treated cells. No effect was observed in cells treated with L L-tocopherol. z 1999 Federation of European Biochemical Societies.
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