Effects of phosphatidylethanolamine glycation on lipid–protein interactions

VALERIA LEVI, ANA M. VILLAMIL GIRALDO, PABLO R. CASTELLO, JUAN P. F. C. ROSSI AND F. LUIS GONZ´ALEZ FLECHA

BIOCHEMICAL JOURNAL

PORTLAND PRESS LTD

Año: 2008 vol. 416 p. 145 - 152

0264-6021

Non-enzymatic glycation of biomolecules has been implicated inthe pathophysiology of aging and diabetes. Among the potentialtargets for glycation are biological membranes, characterized bya complex organization of lipids and proteins interacting andforming domains of different size and stability. In the presentstudy, we analyse the effects of glycation on the interactionsbetween membrane proteins and lipids. The phospholipidaffinity for the transmembrane surface of the PMCA (plasmamembraneCa2+-ATPase) was determined after incubating theprotein or the phospholipids with glucose. Results show thatthe affinity between PMCA and the surrounding phospholipidsdecreases significantly after phosphospholipid glycation, butremains unmodified after glycation of the protein. Furthermore,phosphatidylethanolamine glycation decreases by ∼30% thestability of PMCA against thermal denaturation, suggesting thatglycated aminophospholipids induce a structural rearrangementin the protein that makes it more sensitive to thermal unfolding.We also verified that lipid glycation decreases the affinity of lipidsfor two othermembrane proteins, suggesting that this effect mightbe common to membrane proteins. Extending these results to thein vivo situation, we can hypothesize that, under hyperglycaemicconditions, glycation of membrane lipids may cause a significantchange in the structure and stability of membrane proteins, whichmay affect the normal functioning of membranes and therefore ofcells.