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Identifier 000338032
Title Μηχανισμός δράσης αντιοξειδωτικών σε κυτταρικό επίπεδο
Author Νιφλή, Αρτεμισία-Φοίβη
Thesis advisor Καστανάς, Ηλίας
Reviewer Γραβάνης, Αχιλλέας
Χατζόγλου, Αναστασία
Κατερινόπουλος, Χ.
Κουρούμαλης, Ε.
Μαργιωρής, Α.
Σταθόπουλος, Ε.
Θεοδωρόπουλος, Παναγιώτης
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.
Language Greek
Subject Antioxidants
Issue date 2006-12-20
Collection   Faculty/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
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