The impact of glycation on apolipoprotein A-I structure and its ability to activate lecithin: cholesterol acyltransferase

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Standard

The impact of glycation on apolipoprotein A-I structure and its ability to activate lecithin : cholesterol acyltransferase. / Nobecourt, E.; Davies, M. J.; Brown, B. E.; Curtiss, L. K.; Bonnet, D. J.; Charlton, F.; Januszewski, A. S.; Jenkins, A. J.; Barter, P. J.; Rye, K. -A.

In: Diabetologia, Vol. 50, No. 3, 03.2007, p. 643-653.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Nobecourt, E, Davies, MJ, Brown, BE, Curtiss, LK, Bonnet, DJ, Charlton, F, Januszewski, AS, Jenkins, AJ, Barter, PJ & Rye, K-A 2007, 'The impact of glycation on apolipoprotein A-I structure and its ability to activate lecithin: cholesterol acyltransferase', Diabetologia, vol. 50, no. 3, pp. 643-653. https://doi.org/10.1007/s00125-006-0574-z

APA

Nobecourt, E., Davies, M. J., Brown, B. E., Curtiss, L. K., Bonnet, D. J., Charlton, F., Januszewski, A. S., Jenkins, A. J., Barter, P. J., & Rye, K. -A. (2007). The impact of glycation on apolipoprotein A-I structure and its ability to activate lecithin: cholesterol acyltransferase. Diabetologia, 50(3), 643-653. https://doi.org/10.1007/s00125-006-0574-z

Vancouver

Nobecourt E, Davies MJ, Brown BE, Curtiss LK, Bonnet DJ, Charlton F et al. The impact of glycation on apolipoprotein A-I structure and its ability to activate lecithin: cholesterol acyltransferase. Diabetologia. 2007 Mar;50(3):643-653. https://doi.org/10.1007/s00125-006-0574-z

Author

Nobecourt, E. ; Davies, M. J. ; Brown, B. E. ; Curtiss, L. K. ; Bonnet, D. J. ; Charlton, F. ; Januszewski, A. S. ; Jenkins, A. J. ; Barter, P. J. ; Rye, K. -A. / The impact of glycation on apolipoprotein A-I structure and its ability to activate lecithin : cholesterol acyltransferase. In: Diabetologia. 2007 ; Vol. 50, No. 3. pp. 643-653.

Bibtex

@article{6b1f9ac53b5544409908573feea1c81f,
title = "The impact of glycation on apolipoprotein A-I structure and its ability to activate lecithin: cholesterol acyltransferase",
abstract = "Aims/hypothesis Hyperglycaemia, one of the main features of diabetes, results in non-enzymatic glycation of plasma proteins, including apolipoprotein A-I (apoA-I), the most abundant apolipoprotein in HDL. The aim of this study was to determine how glycation affects the structure of apoA-I and its ability to activate lecithin:cholesterol acyltransferase (LCAT), a key enzyme in reverse cholesterol transport.Materials and methods Discoidal reconstituted HDL (rHDL) containing phosphatidylcholine and apoA-I ([A-I]rHDL) were prepared by the cholate dialysis method and glycated by incubation with methylglyoxal. Glycation of apoA-I was quantified as the reduction in detectable arginine, lysine and tryptophan residues. Methylglyoxal-AGE adduct formation in apoA-I was assessed by immunoblotting. (A-I)rHDL size and surface charge were determined by non-denaturing gradient gel electrophoresis and agarose gel electrophoresis, respectively. The kinetics of the LCAT reaction was investigated by incubating varying concentrations of discoidal (A-I)rHDL with a constant amount of purified enzyme. The conformation of apoA-I was assessed by surface plasmon resonance.Results Methylglyoxal-mediated modifications of the arginine, lysine and tryptophan residues in lipid-free and lipid-associated apoA-I were time- and concentration-dependent. These modifications altered the conformation of apoA-I in regions critical for LCAT activation and lipid binding. They also decreased (A-I)rHDL size and surface charge. The rate of LCAT-mediated cholesterol esterification in (A-I)rHDL varied according to the level of apoA-I glycation and progressively decreased as the extent of apoA-I glycation increased.Conclusions/interpretation It is concluded that glycation of apoA-I may adversely affect reverse cholesterol transport in subjects with diabetes.",
keywords = "apolipoprotein A-I, diabetes, high-density lipoproteins, lecithin : cholesterol acyltransferase, non-enzymatic glycation, HIGH-DENSITY-LIPOPROTEINS, NONENZYMATIC GLYCOSYLATION, MICELLAR COMPLEXES, DIABETES-MELLITUS, METHYLGLYOXAL, PROTEINS, BINDING, VITRO, AGE, HDL",
author = "E. Nobecourt and Davies, {M. J.} and Brown, {B. E.} and Curtiss, {L. K.} and Bonnet, {D. J.} and F. Charlton and Januszewski, {A. S.} and Jenkins, {A. J.} and Barter, {P. J.} and Rye, {K. -A.}",
year = "2007",
month = mar,
doi = "10.1007/s00125-006-0574-z",
language = "English",
volume = "50",
pages = "643--653",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer",
number = "3",

}

RIS

TY - JOUR

T1 - The impact of glycation on apolipoprotein A-I structure and its ability to activate lecithin

T2 - cholesterol acyltransferase

AU - Nobecourt, E.

AU - Davies, M. J.

AU - Brown, B. E.

AU - Curtiss, L. K.

AU - Bonnet, D. J.

AU - Charlton, F.

AU - Januszewski, A. S.

AU - Jenkins, A. J.

AU - Barter, P. J.

AU - Rye, K. -A.

PY - 2007/3

Y1 - 2007/3

N2 - Aims/hypothesis Hyperglycaemia, one of the main features of diabetes, results in non-enzymatic glycation of plasma proteins, including apolipoprotein A-I (apoA-I), the most abundant apolipoprotein in HDL. The aim of this study was to determine how glycation affects the structure of apoA-I and its ability to activate lecithin:cholesterol acyltransferase (LCAT), a key enzyme in reverse cholesterol transport.Materials and methods Discoidal reconstituted HDL (rHDL) containing phosphatidylcholine and apoA-I ([A-I]rHDL) were prepared by the cholate dialysis method and glycated by incubation with methylglyoxal. Glycation of apoA-I was quantified as the reduction in detectable arginine, lysine and tryptophan residues. Methylglyoxal-AGE adduct formation in apoA-I was assessed by immunoblotting. (A-I)rHDL size and surface charge were determined by non-denaturing gradient gel electrophoresis and agarose gel electrophoresis, respectively. The kinetics of the LCAT reaction was investigated by incubating varying concentrations of discoidal (A-I)rHDL with a constant amount of purified enzyme. The conformation of apoA-I was assessed by surface plasmon resonance.Results Methylglyoxal-mediated modifications of the arginine, lysine and tryptophan residues in lipid-free and lipid-associated apoA-I were time- and concentration-dependent. These modifications altered the conformation of apoA-I in regions critical for LCAT activation and lipid binding. They also decreased (A-I)rHDL size and surface charge. The rate of LCAT-mediated cholesterol esterification in (A-I)rHDL varied according to the level of apoA-I glycation and progressively decreased as the extent of apoA-I glycation increased.Conclusions/interpretation It is concluded that glycation of apoA-I may adversely affect reverse cholesterol transport in subjects with diabetes.

AB - Aims/hypothesis Hyperglycaemia, one of the main features of diabetes, results in non-enzymatic glycation of plasma proteins, including apolipoprotein A-I (apoA-I), the most abundant apolipoprotein in HDL. The aim of this study was to determine how glycation affects the structure of apoA-I and its ability to activate lecithin:cholesterol acyltransferase (LCAT), a key enzyme in reverse cholesterol transport.Materials and methods Discoidal reconstituted HDL (rHDL) containing phosphatidylcholine and apoA-I ([A-I]rHDL) were prepared by the cholate dialysis method and glycated by incubation with methylglyoxal. Glycation of apoA-I was quantified as the reduction in detectable arginine, lysine and tryptophan residues. Methylglyoxal-AGE adduct formation in apoA-I was assessed by immunoblotting. (A-I)rHDL size and surface charge were determined by non-denaturing gradient gel electrophoresis and agarose gel electrophoresis, respectively. The kinetics of the LCAT reaction was investigated by incubating varying concentrations of discoidal (A-I)rHDL with a constant amount of purified enzyme. The conformation of apoA-I was assessed by surface plasmon resonance.Results Methylglyoxal-mediated modifications of the arginine, lysine and tryptophan residues in lipid-free and lipid-associated apoA-I were time- and concentration-dependent. These modifications altered the conformation of apoA-I in regions critical for LCAT activation and lipid binding. They also decreased (A-I)rHDL size and surface charge. The rate of LCAT-mediated cholesterol esterification in (A-I)rHDL varied according to the level of apoA-I glycation and progressively decreased as the extent of apoA-I glycation increased.Conclusions/interpretation It is concluded that glycation of apoA-I may adversely affect reverse cholesterol transport in subjects with diabetes.

KW - apolipoprotein A-I

KW - diabetes

KW - high-density lipoproteins

KW - lecithin : cholesterol acyltransferase

KW - non-enzymatic glycation

KW - HIGH-DENSITY-LIPOPROTEINS

KW - NONENZYMATIC GLYCOSYLATION

KW - MICELLAR COMPLEXES

KW - DIABETES-MELLITUS

KW - METHYLGLYOXAL

KW - PROTEINS

KW - BINDING

KW - VITRO

KW - AGE

KW - HDL

U2 - 10.1007/s00125-006-0574-z

DO - 10.1007/s00125-006-0574-z

M3 - Journal article

VL - 50

SP - 643

EP - 653

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 3

ER -

ID: 314392458