Membrane cholesterol content is a major factor that affects the ability of epigallocatechin gallate to inhibit AChE

SALAZAR, PAULA BELÉN; DE ATHAYDE MONCORVO COLLADO, ALEJANDRO; DUPUY, FERNANDO G.; MINAHK, CARLOS

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Polyphenols are plant secondary metabolites able to interact not only with proteins but also with membrane lipids, what may be related with some of the beneficial properties attributable to these compounds.We have already demonstrated that epigallocatechin gallate (EGCG) was efficient as acetylcholinesterase (AChE) inhibitor when the enzyme was bound to membranes. Even though EGCG was still able to inhibit AChE in its soluble form, the effect was less pronounced. In fact, the erythrocyte AChE isoform has proved to be a good model for studying the enzymatic activity of membrane-bound AChE isoforms, hence this variant was chosen to carry out the present work.The activity of AChE, as well as others membrane-bound enzymes, has been shown to depend on membrane lipid composition and order. That is to say, membrane lipid alterations may induce changes in the activities of these enzymes. Therefore, we studied cholesterol-levels influence in erythrocyte membranes on the AChE inhibition by EGCG. In other words, we aimed to know if the interaction of EGCG with membrane varies and if it influences on AChE inhibition degree.EGCG-mediated inhibition of enzymatic activity was enhanced when AChE was bound to membranes with low cholesterol level. The EGCG localization was studied by biophysical techniques. On one hand, an enhanced quenching of rhodamine R-18 fluorescence by EGCG, was observed when cholesterol content of membranes was reduced, leading us to hypothesize that EGCG might interact with interfacial portion of membranes. On the other, possible deeper localization of EGCG in membrane was assessed by IR spectroscopy.It can be concluded that interactions among EGCG and lipid components of membranes are noteworthy since they can determine the inhibitory effect of this polyphenol on membrane bound enzymes.