Effect of the nonenzymatic glycosylation of high density lipoprotein-3 on the cholesterol ester transfer protein activity.
This study examines the relationship between high density lipoprotein-3 (HDL-3) glycation and cholesteryl ester transfer mediated by cholesteryl ester transfer protein (CETP). HDL-3 were glycated with various glucose concentrations (0-200 mM) for 3 d at 37 degrees C with sodium cyanoborohydride as reducing agent and antioxidants. About 47% of the lysine residues were glycated in the presence of 200 mM glucose, resulting in an increase in the cholesterol ester (CE) transfer of about 30%. Apparent kinetic parameters [expressed as maximal transfer (appT(max)) and CE concentration at half of T(max)(appK(H))] of CETP activity with glycated HDL-3 showed conflicting and paradoxical data: an increase in CETP activity associated with a decrease of CETP affinity. These alterations were not due to a change in HDL-3 lipid and protein composition nor to a peroxidative process but were associated with an increase in HDL-3 electronegativity and a decrease of HDL-3 fluidity. This study suggests that glycation modifies the apolipoprotein's conformation and solvation which are major determinants of interfacial properties of HDL-3. These modifications in turn affect CETP reactivity.
Lemkadem
B
B
Laboratoire de Biochimie et de Biologie Moléculaire, CHU Angers, France.
Loiseau
D
D
Larcher
G
G
Malthiery
Y
Y
Foussard
F
F
D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000378:metabolism; D005454:Fluorescence Polarization; D005947:Glucose / Q000494:pharmacology; D006023:Glycoproteins; D006031:Glycosylation; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000737:chemistry*; D053440:Lipoproteins, HDL3; D008239:Lysine / Q000378:metabolism; D008560:Membrane Fluidity; D011487:Protein Conformation; D055672:Static Electricity
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D005947:Glucose; D008239:Lysine