RRR-alpha-tocopherol regulation of gene transcription in response to the cell oxidant status

Azzi A., Boscoboinik D., Fazzio A., Marilley D., Maroni P., Ozer N., ...More

ZEITSCHRIFT FUR ERNAHRUNGSWISSENSCHAFT, vol.37, pp.21-28, 1998 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 37
  • Publication Date: 1998
  • Journal Name: ZEITSCHRIFT FUR ERNAHRUNGSWISSENSCHAFT
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.21-28
  • Keywords: RRR-alpha-tocopherol, smooth muscle cell proliferation, protein kinase C, arteriosclerosis AP-1, transcription factor, antioxidants, PROTEIN-KINASE-C, SMOOTH-MUSCLE CELL, VITAMIN-E CONSUMPTION, ATHEROSCLEROSIS, PROLIFERATION, PATHOGENESIS, INHIBITION, DISEASE, RISK, ANTIOXIDANTS
  • Marmara University Affiliated: Yes

Abstract

RRR-alpha-Tocopherol, but not RRR-beta-tocopherol, negative regulates proliferation of vascular smooth muscle cells at physiological concentrations. At the same concentrations RRR-alpha-tocopherol inhibits protein kinase C activity, whereas RRR-beta-tocopherol is ineffective. Furthermore, RRR-beta-tocopherol prevents the inhibition of cell growth and of protein kinase C activity caused by RRR-alpha-tocopherol. The negative regulation by RRR-alpha-tocopherol of protein kinase C activity appears to be the cause of smooth muscle cell growth inhibition. RRR-alpha-Tocopherol does not act by binding to protein kinase C directly but presumably by preventing protein kinase C activation. A second RRR-alpha-tocopherol effect has been found at the level of AP 1, the latter becoming activated by RRR-alpha tocopherol under condition of protein kinase C inhibition or down regulation. AP-1 inhibition by RRR-alpha-tocopherol is seen, however, under condition of protein kinase C stimulation. Compositional changes of AP-1 have been found to be at the basis of the RRR-alpha-tocopherol effects. RRR-beta-Tocopherol, provided with similar antioxidant properties, not only it does not affect AP 1 but it prevents the effects of RRR-alpha-tocopherol. Moreover, it has been observed that RRR-alpha-tocopherol is able to affect TRE regulated gene transcription. It concluded that RRR-alpha-tocopherol acts specifically in vascular smooth muscle cells, by controlling a signal transduction pathway leading to cell proliferation by a non-antioxidant mechanism.