tailieunhanh - Báo cáo khoa học: Glycation and glycoxidation of low-density lipoproteins by glucose and low-molecular mass aldehydes Formation of modified and oxidized particles

Patients with diabetes mellitus suffer from an increased incidence of complications including cardiovascular disease and cataracts; the mechanisms responsible for this are not fully understood. One characteristic of such complications is an accumulation of advanced glycation end-products formed by the adduction of glucose or species derived from glucose, such as low-molecular mass aldehydes, to proteins. | Eur. J. Biochem. 270 3572-3582 2003 FEBS 2003 doi Glycation and glycoxidation of low-density lipoproteins by glucose and low-molecular mass aldehydes Formation of modified and oxidized particles Heather M. Knott Bronwyn E. Brown Michael J. Davies and Roger T. Deant The Heart Research Institute Camperdown Australia Patients with diabetes mellitus suffer from an increased incidence of complications including cardiovascular disease and cataracts the mechanisms responsible for this are not fully understood. One characteristic of such complications is an accumulation of advanced glycation end-products formed by the adduction of glucose or species derived from glucose such as low-molecular mass aldehydes to proteins. These reactions can be nonoxidative glycation or oxidaií ve glycoxidation and result in the conversion of low-density lipoproteins LDL to a form hhat is recggnieed by ffte scavenger receptors of macrophages. This results in the accumulation of cholesterol and cholesteryl esters within macrophages and the formation of foam cells a hallmark of atherosclerosis. The nature of the LDL modifications required for cellular recognition and unregulated uptake are poorly understood. We have therefore examined the nature time course and extent of LDL modifications induced by glucose and two aldehydes methylglyoxal and glycolaldehyde. It has been shown that these agents modify Arg Lys and Trp residues of the apoB protein of LDL with the extent of modification induced by the two aldehydes being more rapid than with glucose. These processes are rapid and unaffected by low concentrations of copper ions. In contrast lipid and protein oxidation are slow processes and occur to a limited extent in the absence of added copper ions. No evidence was obtained for the stimulation of lipid or protein oxidation by glucose or methylglyoxal in the presence of copper ions whereas glycolaldehyde stimulated such reactions to a modest extent. These results .