nach oben

Erschienen in:

01.03.2007 | Article

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

verfasst von: E. Nobecourt, M. J. Davies, B. E. Brown, L. K. Curtiss, D. J. Bonnet, F. Charlton, A. S. Januszewski, A. J. Jenkins, P. J. Barter, K.-A. Rye

Erschienen in: Diabetologia | Ausgabe 3/2007

Einloggen, um Zugang zu erhalten

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.

Gu K, Cowie CC, Harris MI (1999) Diabetes and decline in heart disease mortality in US adults. JAMA 281:1291–1297PubMedCrossRef

Tan KC, Chow WS, Ai VH, Metz C, Bucala R, Lam KS (2002) Advanced glycation end products and endothelial dysfunction in type 2 diabetes. Diabetes Care 25:1055–1059PubMed

Lin RY, Reis ED, Dore AT et al (2002) Lowering of dietary advanced glycation endproducts (AGE) reduces neointimal formation after arterial injury in genetically hypercholesterolemic mice. Atherosclerosis 163: 303–311PubMedCrossRef

McLellan AC, Thornalley PJ, Benn J, Sonksen PH (1994) Glyoxalase system in clinical diabetes mellitus and correlation with diabetic complications. Clin Sci 87:21–29PubMed

Lo TW, Westwood ME, McLellan AC, Selwood T, Thornalley PJ (1994) Binding and modification of proteins by methylglyoxal under physiological conditions. A kinetic and mechanistic study with N alpha-acetylarginine, N alpha-acetylcysteine, and N alpha-acetyllysine, and bovine serum albumin. J Biol Chem 269:32299–32305PubMed

Zeng J, Davies MJ (2005) Evidence for the formation of adducts and S-(carboxymethyl)cysteine on reaction of alpha-dicarbonyl compounds with thiol groups on amino acids, peptides, and proteins. Chem Res Toxicol 18:1232–1241PubMedCrossRef

Curtiss LK, Witztum JL (1985) Plasma apolipoproteins AI, AII, B, CI, and E are glucosylated in hyperglycemic diabetic subjects. Diabetes 34:452–461PubMed

Shishino K, Murase M, Makino H, Saheki S (2000) Glycated apolipoprotein A-I assay by combination of affinity chromatography and latex immunoagglutination. Ann Clin Biochem 37:498–506PubMedCrossRef

Winlove CP, Parker KH, Avery NC, Bailey AJ (1996) Interactions of elastin and aorta with sugars in vitro and their effects on biochemical and physical properties. Diabetologia 39:1131–1139PubMed

10.

Che W, Asahi M, Takahashi M et al (1997) Selective induction of heparin-binding epidermal growth factor-like growth factor by methylglyoxal and 3-deoxyglucosone in rat aortic smooth muscle cells. The involvement of reactive oxygen species formation and a possible implication for atherogenesis in diabetes. J Biol Chem 272:18453–18459PubMedCrossRef

11.

Duell PB, Oram JF, Bierman EL (1990) Nonenzymatic glycosylation of HDL resulting in inhibition of high-affinity binding to cultured human fibroblasts. Diabetes 39:1257–1263PubMed

12.

Duell PB, Oram JF, Bierman EL (1991) Nonenzymatic glycosylation of HDL and impaired HDL-receptor-mediated cholesterol efflux. Diabetes 40:377–384PubMed

13.

Witztum JL, Fisher M, Pietro T, Steinbrecher UP, Elam RL (1982) Nonenzymatic glucosylation of high-density lipoprotein accelerates its catabolism in guinea pigs. Diabetes 31:1029–1032PubMed

14.

Passarelli M, Catanozi S, Nakandakare ER et al (1997) Plasma lipoproteins from patients with poorly controlled diabetes mellitus and “in vitro” glycation of lipoproteins enhance the transfer rate of cholesteryl ester from HDL to apo-B-containing lipoproteins. Diabetologia 40: 1085–1093PubMedCrossRef

15.

Quintao EC, Medina WL, Passarelli M (2000) Reverse cholesterol transport in diabetes mellitus. Diabetes Metab Res Rev 16:237–250PubMedCrossRef

16.

Fielding CJ, Shore VG, Fielding PE (1972) A protein cofactor of lecithin:cholesterol acyltransferase. Biochem Biophys Res Commun 46:1493–1498PubMedCrossRef

17.

Ohta T, Nishiyama S, Nakamura T, Saku K, Maung KK, Matsuda I (1998) Predominance of large low density lipoprotein particles and lower fractional esterification rate of cholesterol in high density lipoprotein in children with insulin-dependent diabetes mellitus. Eur J Pediatr 157:276–281PubMedCrossRef

18.

Schernthaner G, Kostner GM, Dieplinger H, Prager R, Muhlhauser I (1983) Apolipoproteins (A-I, A-II, B), Lp(a) lipoprotein and lecithin-cholesterol acyltransferase activity in diabetes-mellitus. Atherosclerosis 49:277–293PubMedCrossRef

19.

Riemens S, van Tol A, Sluiter W, Dullaart R (1998) Elevated plasma cholesteryl ester transfer in NIDDM: relationships with apolipoprotein B-containing lipoproteins and phospholipid transfer protein. Atherosclerosis 140:71–79PubMedCrossRef

20.

Calvo C, Ulloa N, Campos M, Verdugo C, Ayrault-Jarrier M (1993) The preferential site of nonenzymatic glycation of human apolipoprotein-A-I in-vivo. Clin Chim Acta 217:193–198PubMedCrossRef

21.

Gugliucci A, Stahl AJ (1991) In vitro glycation of human apolipoprotein AI reduces its efficiency in lecithin:cholesterol acyltransferase activation. Clin Chim Acta 204:37–42PubMedCrossRef

22.

Fournier N, Myara I, Atger V, Moatti N (1995) Reactivity of lecithin-cholesterol acyl transferase (LCAT) towards glycated high-density lipoproteins (HDL). Clin Chim Acta 234:47–61PubMedCrossRef

23.

Rye KA, Garrety KH, Barter PJ (1993) Preparation and characterization of spheroidal, reconstituted high-density lipoproteins with apolipoprotein A-I only or with apolipoprotein A-I and A-II. Biochim Biophys Acta 1167:316–325PubMed

24.

Osborne JC Jr (1986) Delipidation of plasma lipoproteins. Methods Enzymol 128:213–222PubMed

25.

Weisweiler P (1987) Isolation and quantitation of apolipoproteins A-I and A-II from human high-density lipoproteins by fast-protein liquid chromatography. Clin Chim Acta 169:249–254PubMedCrossRef

26.

Matz CE, Jonas A (1982) Micellar complexes of human apolipoprotein A-I with phosphatidylcholines and cholesterol prepared from cholate-lipid dispersions. J Biol Chem 257:4535–4540PubMed

27.

Piran U, Morin RJ (1979) A rapid radioassay procedure for plasma lecithin-cholesterol acyltransferase. J Lipid Res 20:1040–1043PubMed

28.

Knott HM, Brown BE, Davies MJ, Dean RT (2003) Glycation and glycoxidation of low-density lipoproteins by glucose and low-molecular mass aldehydes. Formation of modified and oxidized particles. Eur J Biochem 270:3572–3582PubMedCrossRef

29.

Sparks DL, Phillips MC (1992) Quantitative measurement of lipoprotein surface charge by agarose gel electrophoresis. J Lipid Res 33:123–130PubMed

30.

Curtiss LK, Bonnet DJ, Rye KA (2000) The conformation of apolipoprotein A-I in high-density lipoproteins is influenced by core lipid composition and particle size: a surface plasmon resonance study. Biochemistry 39:5712–5721PubMedCrossRef

31.

Rawn JD (1989) Enzyme catalysis and enzyme kinetics. In: Biochemistry, Int Ed. Neil Patterson, Burlington, NC, pp 148–193

32.

Takayama M, Itoh S, Nagasaki T, Tanimizu I (1977) A new enzymatic method for determination of serum choline-containing phospholipids. Clin Chim Acta 79:93–98PubMedCrossRef

33.

Stahler F, Gruber W, Stinshoff K, Roschlau P (1977) A practical enzymatic cholesterol determination. Med Lab 30:29–37

34.

Smith PK, Krohn RI, Hermanson GT et al (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150:76–85PubMedCrossRef

35.

Rainwater DL, Andres DW, Ford AL, Lowe F, Blanche PJ, Krauss RM (1992) Production of polyacrylamide gradient gels for the electrophoretic resolution of lipoproteins. J Lipid Res 33:1876–1881PubMed

36.

Dunn JA, McCance DR, Thorpe SR, Lyons TJ, Baynes JW (1991) Age-dependent accumulation of N epsilon-(carboxymethyl)lysine and N epsilon-(carboxymethyl)hydroxylysine in human skin collagen. Biochemistry 30:1205–1210PubMedCrossRef

37.

Ahmed MU, Brinkmann Frye E, Degenhardt TP, Thorpe SR, Baynes JW (1997) N-epsilon-(carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins. Biochem J 324:565–570PubMed

38.

Dyer DG, Blackledge JA, Thorpe SR, Baynes JW (1991) Formation of pentosidine during nonenzymatic browning of proteins by glucose. Identification of glucose and other carbohydrates as possible precursors of pentosidine in vivo. J Biol Chem 266:11654–11660PubMed

39.

Malmendier CL, Delcroix C, Ameryckx JP (1983) In vivo metabolism of human apoprotein A-I-phospholipid complexes. Comparison with human high density lipoprotein-apoprotein A-I metabolism. Clin Chim Acta 131:201–210PubMedCrossRef

40.

Khaw KT, Wareham N, Luben R et al (2001) Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of European prospective investigation of cancer and nutrition (EPIC-Norfolk). BMJ 322:15–18PubMedCrossRef

41.

Santamarina-Fojo S, Lambert G, Hoeg JM, Brewer HB Jr (2000) Lecithin-cholesterol acyltransferase: role in lipoprotein metabolism, reverse cholesterol transport and atherosclerosis. Curr Opin Lipidol 11:267–275PubMedCrossRef

42.

Lapolla A, Flamini R, Dalla Vedova A et al (2003) Glyoxal and methylglyoxal levels in diabetic patients: quantitative determination by a new GC/MS method. Clin Chem Lab Med 41:1166–1173PubMedCrossRef

43.

McLellan AC, Phillips SA, Thornalley PJ (1992) The assay of methylglyoxal in biological systems by derivatization with 1,2-diamino-4,5-dimethoxybenzene. Anal Biochem 206:17–23PubMedCrossRef

44.

Matz CE, Jonas A (1982) Reaction of human lecithin cholesterol acyltransferase with synthetic micellar complexes of apolipoprotein A-I, phosphatidylcholine, and cholesterol. J Biol Chem 257:4541–4546PubMed

45.

Brown BE, Dean RT, Davies MJ (2005) Glycation of low-density lipoproteins by methylglyoxal and glycolaldehyde gives rise to the in vitro formation of lipid-laden cells. Diabetologia 48:361–369PubMedCrossRef

46.

Alexander ET, Bhat S, Thomas MJ et al (2005) Apolipoprotein A-I helix 6 negatively charged residues attenuate lecithin-cholesterol acyltransferase (LCAT) reactivity. Biochemistry 44:5409–5419PubMedCrossRef

47.

Wong L, Curtiss LK, Huang J, Mann CJ, Maldonado B, Roheim PS (1992) Altered epitope expression of human interstitial fluid apolipoprotein A-I reduces its ability to activate lecithin cholesterol acyl transferase. J Clin Invest 90:2370–2375PubMedCrossRef

48.

Jonas A (1998) Regulation of lecithin cholesterol acyltransferase activity. Prog Lipid Res 37:209–234PubMedCrossRef

49.

Frank PG, Marcel YL (2000) Apolipoprotein A-I: structure-function relationships. J Lipid Res 41:853–872PubMed

50.

McLean LR, Phillips MC (1981) Mechanism of cholesterol and phosphatidylcholine exchange or transfer between unilamellar vesicles. Biochemistry 20 2893–2900PubMedCrossRef

Titel: The impact of glycation on apolipoprotein A-I structure and its ability to activate lecithin:cholesterol acyltransferase
verfasst von: E. Nobecourt
M. J. Davies
B. E. Brown
L. K. Curtiss
D. J. Bonnet
F. Charlton
A. S. Januszewski
A. J. Jenkins
P. J. Barter
K.-A. Rye
Publikationsdatum: 01.03.2007
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 3/2007
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-006-0574-z

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

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