Affiliations: Institut für Biochemie und Molekularbiologie, Universität Bern, Bühlstrasse 28, 3012 Bern, Switzerland | Department of Biochemistry, Marmara University, 81326 Haydarpasa‐Istanbul, Turkey | Istituto di Patologia Generale, Università di Genova, via L.B. Alberti 2, 16132 Genova, Italy
Note: [] To whom correspondence should be addressed.
Abstract: 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 \muM. \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.
Keywords: [TeX:] \alpha‐tocopherol, vitamin E, protein kinase C, vascular smooth muscle cell, cell proliferation, protein phosphatase, oxidative stress
Journal: Biofactors, vol. 7, no. 1-2, pp. 3-14, 1998
