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Effect of the nonenzymatic glycosylation of high density lipoprotein-3 on the cholesterol ester transfer protein activity

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Lipids

Abstract

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°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.

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Abbreviations

apo:

apoprotein

CE:

cholesterol ester

CETP:

cholesterol ester transfer protein

DPH:

1,6-diphenyl-1,3,5-hexatriefe

gHDL-3:

glycated HDL-3

3H-CE:

tritiated cholesterolester

HDL:

high density lipoproteins

K H :

CE-concentration at half T max

LCAT:

lecithin-cholesterol acyl transmellitus

r :

fluorescence anistropy

rHDL:

recombinant HDL

T max :

maximal transfer velocity

TRARS:

throbarbituric acid-reactive strecies

TG:

triacylglyerols

TNBS:

trinitrobenzene-sulfonic acid

UC/PL:

unesterified cholesterol/phospholipid ratio

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Authors and Affiliations

  1. Laboratoire de Biochimie et de Biologie Moléculaire, CHU Angers, 1 rue haute de Reculée Faculté de Médecine, 49045, Angers, France

    B. Lemkadem, D. Loiseau & Y. Malthiery

  2. Laboratoire de Biochimie Faculté de Pharmacie Angers, 1 rue haute de Reculée Faculté de Médecine, 49045, Angers, France

    G. Larcher & F. Foussard

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  1. B. Lemkadem
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  2. D. Loiseau
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  4. Y. Malthiery
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  5. F. Foussard
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Lemkadem, B., Loiseau, D., Larcher, G. et al. Effect of the nonenzymatic glycosylation of high density lipoprotein-3 on the cholesterol ester transfer protein activity. Lipids 34, 1281–1286 (1999). https://doi.org/10.1007/s11745-999-0479-0

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  • DOI: https://doi.org/10.1007/s11745-999-0479-0

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