Interactions of large procyanidins with membranes and the regulation of cell signaling

M. DA SILVA; G. JAGGERS; A. G. ERLEJMAN; C. G. FRAGA; P. I. OTEIZA

Santa Barbara, EEUU

Congreso; Oxygen Club of California 2008 Meeting; 2008

Oxygen Club of California

We have presented evidence that large procyanidins (LP) can interact with membranes and protect intestinal cells from different pro-inflammatory stimuli. We have now tested if LP could prevent the triggering of different events that has been associated to lipid rafts, i.e calcium mobilization, oxidant formation, and activation of select cell signals. To test this hypothesis, we used liposomes, and Caco-2 cells as a model of intestinal epithelium, and investigated the effects of a fraction enriched in LP isolated from cocoa. LP prevented Triton-X 100-mediated disruption of synthetic liposomes enriched with glycoplipids (main components of lipid rafts). In Caco-2 cells, LP inhibited NF-êB activation initiated by different pro-stimulatory compounds, showing the highest inhibitory capacity for signaling initiated at lipid rafts (e.g. tumor necrosis factor alpha). Furthermore, LP inhibited deoxycholate-induced calcium mobilization, oxidant production, and activation of mitogenactivated kinases (MAPKs). In summary, LP can interact with synthetic and biological membranes and protect them from different pro-inflammatory stimuli. The obtained results suggest that LP could have a relative selectivity to interact with particular areas of the membrane, e.g. lipid rafts, and to modulate oxidant and signaling events initiated in these areas.êB activation initiated by different pro-stimulatory compounds, showing the highest inhibitory capacity for signaling initiated at lipid rafts (e.g. tumor necrosis factor alpha). Furthermore, LP inhibited deoxycholate-induced calcium mobilization, oxidant production, and activation of mitogenactivated kinases (MAPKs). In summary, LP can interact with synthetic and biological membranes and protect them from different pro-inflammatory stimuli. The obtained results suggest that LP could have a relative selectivity to interact with particular areas of the membrane, e.g. lipid rafts, and to modulate oxidant and signaling events initiated in these areas.