Interaction of polyphenols with lipid membranes and modulation of key membrane proteins

MINAHK, C; DE ATHAYDE MONCORVO, A; SALAZAR, PB

Banff, Alberta

Conferencia; Bridging discovery research with therapies; 2017

Molecular and Cellular Biology of Lipids (MCBL)

We postulate that polyphenols can alter the activity of membrane transporters and membrane enzymes either by a direct interaction with the proteins involved or indirectly through the binding to the membrane lipids where the proteins are inserted. As a matter of fact, the insertion of resveratrol into the phospholipid bilayer was sufficient to stimulate the ATPase activity of ABCG1. For this reason, we studied the affinity of resveratrol and other polyphenols for biological membranes by means of Langmuir monolayers and liposomes. We demonstrated that some phenolic compounds could be easily inserted into fluid membranes. However, if the membranes were more ordered due to the presence of cholesterol, the polyphenols only bound superficially. This type of association conferred greater stability to membranes. On the contrary, if the polyphenols were inserted into  the hydrophobic region of the phospholipid bilayers, a marked alteration of the physicochemical properties of these membranes took place and a greater antioxidant capacity could be observed. We verified a similar trend in rat liver membranes.In contrast to what was found in liver membranes, no change in ATPase activity was observed when the same compounds were tested on red blood cell membranes. However, we did find an important inhibition of acetylcholinesterase (AChE), a membrane bound enzyme, in the presence of epigallocatechin gallate (EGCG). It was shown that this polyphenol only interacted with the surface of erythrocyte membranes probably because of the high cholesterol content of these structures. Actually, the pre-treatment of red blood cell ghosts with β-methyl cyclodextrin led to a greater inhibition of AChE by EGCG. It is important to mention that the inhibition of AChE was significantly lower when the enzyme was solubilized. These results suggest that EGCG could inhibit more efficiently with AChE if there is a previous interaction with the membrane where this enzyme is bound.