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Non-enzymatic glycation of biomolecules has been implicated in the pathophysiology of aging and diabetes. Among the potential targets for glycation are biological membranes, characterized by a complex organization of lipids and proteins interacting and forming domains of different size and stability. In the present study, we analyse the effects of glycation on the interactions between membrane proteins and lipids. The phospholipid affinity for the transmembrane surface of the PMCA (plasma-membrane Ca2+-ATPase) was determined after incubating the protein or the phospholipids with glucose. Results show that the affinity between PMCA and the surrounding phospholipids decreases significantly after phosphospholipid glycation, but remains unmodified after glycation of the protein. Furthermore, phosphatidylethanolamine glycation decreases by ∼30% the stability of PMCA against thermal denaturation, suggesting that glycated aminophospholipids induce a structural rearrangement in the protein that makes it more sensitive to thermal unfolding. We also verified that lipid glycation decreases the affinity of lipids for two othermembrane proteins, suggesting that this effect might be common to membrane proteins. Extending these results to the in vivo situation, we can hypothesize that, under hyperglycaemic conditions, glycation of membrane lipids may cause a significant change in the structure and stability of membrane proteins, which may affect the normal functioning of membranes and therefore of cells. © The Authors Journal compilation.


Documento: Artículo
Título:Effects of phosphatidylethanolamine glycation on lipid-protein interactions and membrane protein thermal stability
Autor:Levi, V.; Villamil Giraldo, A.M.; Castello, P.R.; Rossi, J.P.F.C.; González Flecha, F.L.
Filiación:Departamento de Física y Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria 1428 Buenos Aires, Argentina
Instituto de Química y Fisicoquímica Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires-CONICET, Junín 956, 1113 Buenos Aires, Argentina
Department of Molecular Cellular and Developmental Biology, University of Colorado at Boulder, Boulder, CO, United States
Palabras clave:Membrane protein; Non-enzymatic glycation; Phospholipid; Plasma membrane Ca2+ - ATPase; Protein-lipid interaction; Different sizes; Glycation; In-vivo; Lipid-protein interactions; Membrane lipids; Membrane protein; Membrane proteins; Non-enzymatic; Non-enzymatic glycation; Pathophysiology; Phosphatidylethanolamine; Plasma membrane Ca2+ - ATPase; Protein-lipid interaction; Structural rearrangement; Thermal denaturations; Thermal unfolding; Transmembrane; Biological membranes; Calcium; Cell membranes; Cytology; Glucose; Molecular biology; Phospholipids; Plasmas; Proteins; Pyrolysis; Stability; Membranes; adenosine triphosphatase (calcium); adenosine triphosphatase (potassium sodium); aminophospholipid; erythrocyte band 3 protein; membrane lipid; membrane protein; phosphatidylethanolamine; phospholipid; 1,2 dimyristoylphosphatidylethanolamine; 1,2-dimyristoylphosphatidylethanolamine; adenosine triphosphatase (potassium sodium); advanced glycation end product; detergent; dimyristoylphosphatidylcholine; erythrocyte band 3 protein; glucose; macrogol derivative; membrane protein; plasma membrane calcium transporting adenosine triphosphatase; polyoxyethylene 10 dodecyl ether; polyoxyethylene-10-dodecyl ether; article; binding affinity; cell surface; controlled study; erythrocyte membrane; glycation; human; human cell; hyperglycemia; lipid composition; membrane structure; priority journal; protein folding; protein glycosylation; protein lipid interaction; protein stability; protein structure; thermostability; animal; blood; chemistry; drug effect; enzyme stability; enzymology; erythrocyte; glycosylation; micelle; protein denaturation; swine; Animals; Anion Exchange Protein 1, Erythrocyte; Detergents; Dimyristoylphosphatidylcholine; Enzyme Stability; Erythrocytes; Glucose; Glycosylation; Glycosylation End Products, Advanced; Humans; Membrane Proteins; Micelles; Phosphatidylethanolamines; Plasma Membrane Calcium-Transporting ATPases; Polyethylene Glycols; Protein Denaturation; Sodium-Potassium-Exchanging ATPase; Swine
Página de inicio:145
Página de fin:152
Título revista:Biochemical Journal
Título revista abreviado:Biochem. J.
CAS:phosphatidylethanolamine, 1405-71-6; dimyristoylphosphatidylcholine, 13699-48-4, 18194-24-6; glucose, 50-99-7, 84778-64-3; 1,2-dimyristoylphosphatidylethanolamine, 20255-95-2; Anion Exchange Protein 1, Erythrocyte; Detergents; Dimyristoylphosphatidylcholine, 13699-48-4; Glucose, 50-99-7; Glycosylation End Products, Advanced; Membrane Proteins; Micelles; phosphatidylethanolamine, 39382-08-6; Phosphatidylethanolamines; Plasma Membrane Calcium-Transporting ATPases, EC; Polyethylene Glycols; polyoxyethylene-10-dodecyl ether; Sodium-Potassium-Exchanging ATPase, EC


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---------- APA ----------
Levi, V., Villamil Giraldo, A.M., Castello, P.R., Rossi, J.P.F.C. & González Flecha, F.L. (2008) . Effects of phosphatidylethanolamine glycation on lipid-protein interactions and membrane protein thermal stability. Biochemical Journal, 416(1), 145-152.
---------- CHICAGO ----------
Levi, V., Villamil Giraldo, A.M., Castello, P.R., Rossi, J.P.F.C., González Flecha, F.L. "Effects of phosphatidylethanolamine glycation on lipid-protein interactions and membrane protein thermal stability" . Biochemical Journal 416, no. 1 (2008) : 145-152.
---------- MLA ----------
Levi, V., Villamil Giraldo, A.M., Castello, P.R., Rossi, J.P.F.C., González Flecha, F.L. "Effects of phosphatidylethanolamine glycation on lipid-protein interactions and membrane protein thermal stability" . Biochemical Journal, vol. 416, no. 1, 2008, pp. 145-152.
---------- VANCOUVER ----------
Levi, V., Villamil Giraldo, A.M., Castello, P.R., Rossi, J.P.F.C., González Flecha, F.L. Effects of phosphatidylethanolamine glycation on lipid-protein interactions and membrane protein thermal stability. Biochem. J. 2008;416(1):145-152.