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Molecular basis of α‐tocopherol control of smooth muscle cell proliferation
Author(s) -
Azzi Angelo,
Aratri Elisabetta,
Boscoboinik Daniel,
Clément Sophie,
Özer Nesrin K.,
Ricciarelli Roberta,
Spycher Stefan
Publication year - 1998
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.5520070102
Subject(s) - protein kinase a , biochemistry , cyclin dependent kinase 2 , kinase , cgmp dependent protein kinase , dephosphorylation , microbiology and biotechnology , protein kinase c , biology , tocopherol , cell growth , protein phosphatase 2 , okadaic acid , chemistry , phosphatase , phosphorylation , vitamin e , antioxidant
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.