| Abstract |
Polyphenols constitute a heterogenous group of plant-derived dietary micronutrients.
Besides their antioxidant properties, they were shown to modulate several molecular
pathways, including kinase and topoisomerase inhibition, acetylase activation and
NFkappaB or AP-1 transcriptional activity. However, limited bioavailability and tenuous
replication of biochemical actions in cellular systems question their efficacy, while current
implements are not adequate to define whereas polyphenols enter the cell and colocalize
with their presumptive molecular targets.
In the present work, we investigated the bioavailbity, as well as the contribution of
monomeric and polymeric grape polyphenolic compounds in cell metabolism and
homeostasis at cellular and systemic level. Polyphenols were studied at physiologically
relevant concentrations, ranging from 10-12 to 10-6 M.
We found that monomeric and condensed polyphenols are rapidly absorbed after
consumption by healthy individuals or administration in epithelia monolayers. They are
transported across plasma membrane through constitutively expressed channels, such as
organic anion transporters and multi-drug resistant protein pumps. In addition, we
demonstrated that polyphenols accumulate promptly but transiently in subcellular
compartments (nucleoli or ER), without intercalating to macromolecules.
Polyphenols exert short- or mid-term actions on cell proliferation and adhesion, depending
on cellular context. Through androgen membrane binding sites, they activate PI3K and FAK
and they further modulate actin cytoskeleton rearrangement and cell migration. Moreover,
polyphenols induce apoptosis via NO/NOS system regulation. Finally, they rapidly induce
p53 hypoacetylation and SIRT1 and ribosomal protein expression. These rapid
transcriptional modifications provide evidences about the role of polyphenols in RNA
metabolism, joint to cell survival or demise.
Our data suggest a complicate but substantial role of dietary polyphenols in cell fate
regulation. These properties could be of potential value in the prevention and treatment of
chronic conditions and diseases.
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Μηχανισμός δράσης αντιοξειδωτικών σε κυτταρικό επίπεδο
