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RRR-alpha-tocopherol regulation of gene transcription in response to the cell oxidant status
Zeitschrift fur Ernahrungswissenschaft
37 Suppl 1
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.
Animals Antioxidants/*pharmacology Aorta/metabolism Cell Division/drug effects Cell Survival/drug effects Cells, Cultured Chloramphenicol O-Acetyltransferase/biosynthesis DNA/biosynthesis Gene Expression Regulation/drug effects Muscle, Smooth, Vascular/cytology/drug effects/*metabolism Protein Kinase C/*metabolism Rats Recombinant Proteins/biosynthesis Stereoisomerism Tetradecanoylphorbol Acetate/pharmacology Thymidine/metabolism Transcription Factor AP-1/metabolism Transcription, Genetic/*drug effects Transfection Vitamin E/chemistry/*pharmacology
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