| Abstract
| - Some of the beneficial effects of moderate wine consumption may be related to the antioxidantproperties of polyphenolic compounds containing tannins, flavonoids, and phenolic acids. Cellularactions have recently been reported and may involve the modulation of transcriptional factors suchas AP-1 (activator protein-1), which controls the expression of various genes implicated ininflammation processes, cell differentiation, and proliferation. The aim of this study was to evaluatethe modulation of AP-1 activity by the phenolic acids (gallic, caffeic, protocatechic, paracoumaric,sinapic, and ferulic acids) that are present in wine and to compare their modulating pathways tothose of lipophilic or hydrophilic “chain-breaking” antioxidants (such as dl-α-tocopherol or trolox)vitamin C, nitric oxide, and reduced glutathione. AP-1 response was studied on a cell line (MTLN)derived from MCF-7 cells transfected with luciferase gene under TRE sequence control. Afterstimulation by phorbol 12-myristate 13-acetate (PMA; 100 nM, 6 h, 10-7 M), luciferase activity wasdetermined by a luminescence method in the presence of luciferine/coenzyme A solution using aluminometer (LKB 1251, Finland). Antioxidants to be tested were incubated with cells in the presenceor absence of PMA. Stimulation with PMA resulted in an AP-1-mediated increase in luciferase geneexpression corresponding to an 8-fold increase in luciferase activity. After stimulation by PMA, adose-dependent inhibition of AP-1 was observed with the six phenolic acids in the 20 nM−20 μMconcentration range: gallic acid > caffeic > protocatechic, paracoumaric, sinapic acids > ferulicacid. Inhibition was more pronounced with phenolic acids than with dl-α-tocopherol (IC50 = 5 ±4.5 μM for gallic acid vs 85 ± 11 μM for vitamin E). None of the hydrophilic antioxidants inhibitedPMA-induced AP-1 activation. None of the antioxidants tested in the absence of PMA stimulationinduced any activation or inhibition of AP-1. Our results suggest that phenolic acids may act directlyon cell signaling via inhibition of AP-1 transcriptional activity. In addition to preventing LDLoxidation in the arterial wall, our observations indicate that phenolic acids have a cell-mediatedcapacity to prevent some of the processes involved in atherosclerosis in a plasma concentrationrange compatible with nutritional intakes. Keywords: AP-1 transcriptional factor; red wine antioxidants; atherosclerosis
|
