Title
Effect of methylglyoxal on the physico-chemical and biological properties of low-density lipoprotein
Author
Schalkwijk, C.G.
Vermeer, M.A.
Stehouwer, C.D.A.
te Koppele, J.
Princen, H.M.G.
van Hinsbergh, V.W.M.
Gaubius Instituut TNO
Publication year
1998
Abstract
In patients with diabetes, non-enzymatic glycation of low-density lipoprotein (LDL) has been suggested to be involved in the development of atherosclerosis. α-Dicarbonyl compounds were identified as intermediates in the non-enzymatic glycation and increased levels were reported in patients with diabetes. We studied the effect of the α-dicarbonyl compound methylglyoxal (MG) on the physicochemical and biological properties of LDL. MG dose-dependently modifies LDL, as indicated by the formation of fluorescent products and the increase of a net negative charge. MG (10 mmol/l) induced major modifications of arginine residues (up to 85%) and minor lysine modifications (less than 6%). MG-LDL preparations generated small amounts of superoxide anion radicals as measured by the reduction of cytochrome c, but this was not accompanied by peroxidation of the polyunsaturated fatty acids of MG-LDL. MG-LDL showed diminished recognition and uptake by the human LDL receptor in cultured cells and a markedly increased plasma clearance rate in vivo in rats. The reduced association and degradation of 125I-oxidised LDL by murine macrophages indicates recognition of MG-LDL by a scavenger receptor. Surprisingly, MG-LDL caused significantly less cholesteryl ester synthesis in murine macrophages, as compared to native LDL and oxidised or acetylated LDL. Highly modified MG-LDL did not induce activation of human endothelial cells, as measured by the expression of monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1. Copyright (C) 1998 Elsevier Science B.V.
Subject
Biology
Advanced glycation end product
Diabetes
Low density lipoprotein
Methylglyoxal
Arginine
Cholesterol ester
Cytochrome c
Iodine 125
Low density lipoprotein
Low density lipoprotein receptor
Lysine
Methylglyoxal
Monocyte chemotactic protein 1
Oxidized low density lipoprotein
Superoxide
Vasculotropin
Controlled study
Fluorescence
Human
Human cell
Isotope labeling
Lipid metabolism
Macrophage
Plasma clearance
Priority journal
Receptor affinity
Animals
Cell Line
Chemistry, Physical
Cytochrome c Group
Electrochemistry
Endothelium, Vascular
Fibroblasts
Humans
Lipid Peroxidation
Lipid Peroxides
Lipoproteins, LDL
Macrophages
Malondialdehyde
Mice
Oxidation-Reduction
Pyruvaldehyde
Receptors, LDL
Superoxides
Thiobarbituric Acid Reactive Substances
Murinae
To reference this document use:
http://resolver.tudelft.nl/uuid:64d4f1f0-c7ca-4e90-ab1b-14ab67ed4f78
DOI
https://doi.org/10.1016/s0005-2760(98)00112-x
TNO identifier
234668
ISSN
0005-2760
Source
Biochimica et Biophysica Acta - Lipids and Lipid Metabolism, 1394 (2-3), 187-198
Document type
article