Hydrazine compounds inhibit glycation of low-density lipoproteins and prevent the in vitro formation of model foam cells from glycolaldehyde-modified low-density lipoproteins.

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dc.contributor.author Brown, BE
dc.contributor.author Mahroof, FM
dc.contributor.author Cook, NL
dc.contributor.author van Reyk, DM
dc.contributor.author Davies, MJ
dc.date.accessioned 2009-12-21T02:34:22Z
dc.date.issued 2006-04
dc.identifier.citation Diabetologia, 2006, 49 (4), pp. 775 - 783
dc.identifier.issn 0012-186X
dc.identifier.other C1 en_US
dc.identifier.uri http://hdl.handle.net/10453/4678
dc.description.abstract AIMS/HYPOTHESIS: Previous studies have shown that glycation of LDL by methylglyoxal and glycolaldehyde, in the absence of significant oxidation, results in lipid accumulation in macrophage cells. Such 'foam cells' are a hallmark of atherosclerosis. In this study we examined whether LDL glycation by methylglyoxal or glycolaldehyde, and subsequent lipid loading of cells, can be inhibited by agents that scavenge reactive carbonyls. Such compounds may have therapeutic potential in diabetes-associated atherosclerosis. MATERIALS AND METHODS: LDL was glycated with methylglyoxal or glycolaldehyde in the absence or presence of metformin, aminoguanidine, Girard's reagents P and T, or hydralazine. LDL modification was characterised by changes in mobility (agarose gel electrophoresis), cross-linking (SDS-PAGE) and loss of amino acid residues (HPLC). Accumulation of cholesterol and cholesteryl esters in murine macrophages was assessed by HPLC. RESULTS: Inhibition of LDL glycation was detected with equimolar or greater concentrations of the scavengers over the reactive carbonyl. This inhibition was structure-dependent and accompanied by a modulation of cholesterol and cholesteryl ester accumulation. With aminoguanidine, Girard's reagent P and hydralazine, cellular sterol levels returned to control levels despite incomplete inhibition of LDL modification. CONCLUSIONS/INTERPRETATION: Inhibition of LDL glycation by interception of the reactive aldehydes that induce LDL modification prevents lipid loading and model foam cell formation in murine macrophage cells. Carbonyl-scavenging reagents, such as hydrazines, may therefore help inhibit LDL glycation in vivo and prevent diabetes-induced atherosclerosis.
dc.format Print-Electronic
dc.language eng
dc.relation.hasversion Accepted manuscript version en_US
dc.relation.isbasedon 10.1007/s00125-006-0137-3
dc.rights The original publication is available at www.springerlink.com en_US
dc.subject Animals, Mice, Foam Cells, Cell Line, Acetaldehyde, Hydrazines, Lipoproteins, LDL, Glycosylation, Molecular Structure, Models, Biological, Acetaldehyde, Animals, Cell Line, Foam Cells, Glycosylation, Hydrazines, Lipoproteins, LDL, Mice, Models, Biological, Molecular Structure, aldehydes, apolipoprotein B, atherosclerosis, cholesterol esters, foam cells, glycation, hydrazines, low-density lipoproteins, macrophages, protein modification, Endocrinology & Metabolism
dc.subject Animals; Mice; Foam Cells; Cell Line; Acetaldehyde; Hydrazines; Lipoproteins, LDL; Glycosylation; Molecular Structure; Models, Biological; Acetaldehyde; Animals; Cell Line; Foam Cells; Glycosylation; Hydrazines; Lipoproteins, LDL; Mice; Models, Biological; Molecular Structure; aldehydes; apolipoprotein B; atherosclerosis; cholesterol esters; foam cells; glycation; hydrazines; low-density lipoproteins; macrophages; protein modification; Endocrinology & Metabolism
dc.title Hydrazine compounds inhibit glycation of low-density lipoproteins and prevent the in vitro formation of model foam cells from glycolaldehyde-modified low-density lipoproteins.
dc.type Journal Article
dc.parent Diabetologia
dc.journal.volume 4
dc.journal.volume 49
dc.journal.number 4 en_US
dc.publocation New York, USA en_US
dc.identifier.startpage 775 en_US
dc.identifier.endpage 783 en_US
dc.cauo.name SCI.Medical and Molecular Biosciences en_US
dc.conference Verified OK en_US
dc.for 1103 Clinical Sciences
dc.personcode 0000028296 en_US
dc.personcode 0000027765 en_US
dc.personcode 0000027766 en_US
dc.personcode 000788 en_US
dc.personcode 0000045917 en_US
dc.percentage 100 en_US
dc.classification.name Clinical Sciences en_US
dc.classification.type FOR-08 en_US
dc.description.keywords aldehydes; apolipoprotein B; atherosclerosis; cholesterol esters; foam cells; glycation; hydrazines; low-density lipoproteins; macrophages; protein modification en_US
dc.description.keywords Cell Line
dc.description.keywords Foam Cells
dc.description.keywords Animals
dc.description.keywords Mice
dc.description.keywords Acetaldehyde
dc.description.keywords Hydrazines
dc.description.keywords Lipoproteins, LDL
dc.description.keywords Molecular Structure
dc.description.keywords Glycosylation
dc.description.keywords Models, Biological
dc.description.keywords Animals
dc.description.keywords Mice
dc.description.keywords Foam Cells
dc.description.keywords Cell Line
dc.description.keywords Acetaldehyde
dc.description.keywords Hydrazines
dc.description.keywords Lipoproteins, LDL
dc.description.keywords Glycosylation
dc.description.keywords Molecular Structure
dc.description.keywords Models, Biological
pubs.embargo.period Not known
pubs.organisational-group /University of Technology Sydney
pubs.organisational-group /University of Technology Sydney/Faculty of Science
pubs.organisational-group /University of Technology Sydney/Faculty of Science/School of Medical and Molecular Sciences


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