Molecular basis of α‐tocopherol control of smooth muscle cell proliferation

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Abstract
Rat and human vascular smooth muscle cell proliferation is specifically sensitive to α-tocopherol, but not β-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 μM. β-tocopherol addition together with α-tocopherol, prevents both cell growth and protein kinase C inhibition. α-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 α-tocopherol. Experiments with protein kinase C isoform-specific inhibitors and precipitating antibodies show that the only isoform affected by α-tocopherol is protein kinase C-α. The effect of α-tocopherol is prevented by okadaic acid indicating a phosphatase of the PP2A type as responsible for protein kinase C-α dephosphorylation produced in the presence of α-tocopherol. At a gene level α-tocopherol but not β-tocopherol induces a transient activation of α-tropomyosin gene transcription and protein expression. It is proposed that, by inhibiting protein kinase C activity via an activation of a phosphatase PP2A, α-tocopherol controls smooth muscle cell proliferation through changes in gene expression.