Modulation of ATPase activity of liposome-reconstituted ABCG1 by polyphenols

DE ATHAYDE MONCORVO COLLADO A; MORERO RD; MINAHK CJ

Congreso; XLI Reunión Anula de la Sociedad Argentina de Biofísica; 2012

ABCG1 is a half-sized transporter with an unquestionable importance in cholesterol homeostasis. So far, its activity was suggested to be regulated at transcriptional level by LXR and PPARs agonists including polyphenols. But it is unknown whether there are other mechanisms of up-regulation of ABCG1 activity.Human ABCG1 was expressed in the protease deficient strain Saccharomyces cerevisiae BJ2168, purified and reconstituted in proteoliposomes. ATPase activity was estimated in the presence of the polyphenol resveratrol. Membrane fluidity and changes in membrane properties and tryptophan environment were analyzed by fluorometric measurements.Resveratrol was shown to induce a nearly 2-fold increase in ATPase activity of reconstituted ABCG1 and was also able to increase membrane viscosity and polarity of the interphase in a concentration dependent manner; but no correlation with activity change was found. Close interaction ABCG1-resveratrol is suggested from tryptophan emission spectra. Evidence is presented for the first time that resveratrol might be able to activate ABCG1 by an alternative mechanism.This work provides the foundation for the future implementation of this strategy in the evaluation of compounds on ABCG1 activity, enabling a quick and reliable identification of potentially active substances by in vitro activity assays. Therefore, it would speed up the finding of chemicals with potential beneficial cardiovascular properties.