Molecular basis of alpha-tocopherol control of smooth muscle cell proliferation


Azzi A., Aratri E., Boscoboinik D., Clement S., Ozer N., Ricciarelli R., ...Daha Fazla

BIOFACTORS, cilt.7, ss.3-14, 1998 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 7
  • Basım Tarihi: 1998
  • Doi Numarası: 10.1002/biof.5520070102
  • Dergi Adı: BIOFACTORS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.3-14
  • Anahtar Kelimeler: alpha-tocopherol, vitamin E, protein kinase C, vascular smooth muscle cell, cell proliferation, protein phosphatase, oxidative stress
  • Marmara Üniversitesi Adresli: Evet

Özet

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 mu M. 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.