Print Email Facebook Twitter Effect of methylglyoxal on the physico-chemical and biological properties of low-density lipoprotein 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 BiologyAdvanced glycation end productDiabetesLow density lipoproteinMethylglyoxalArginineCholesterol esterCytochrome cIodine 125Low density lipoproteinLow density lipoprotein receptorLysineMethylglyoxalMonocyte chemotactic protein 1Oxidized low density lipoproteinSuperoxideVasculotropinControlled studyFluorescenceHumanHuman cellIsotope labelingLipid metabolismMacrophagePlasma clearancePriority journalReceptor affinityAnimalsCell LineChemistry, PhysicalCytochrome c GroupElectrochemistryEndothelium, VascularFibroblastsHumansLipid PeroxidationLipid PeroxidesLipoproteins, LDLMacrophagesMalondialdehydeMiceOxidation-ReductionPyruvaldehydeReceptors, LDLSuperoxidesThiobarbituric Acid Reactive SubstancesMurinae 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 Files To receive the publication files, please send an e-mail request to TNO Library.