RRR-alpha-tocopherol regulation of gene transcription in response to the cell oxidant status.
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 is 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.
Azzi
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A
Institut für Biochemie und, Molekularbiologie, Universität Bern, Schweiz.
Boscoboinik
D
D
Fazzio
A
A
Marilley
D
D
Maroni
P
P
Ozer
N K
NK
Spycher
S
S
Tasinato
A
A
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D013237:Stereoisomerism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014810:Vitamin E / Q000737:chemistry / Q000494:pharmacology*
D000975:Antioxidants; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D014810:Vitamin E; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine