甲基乙二醛对低密度脂蛋白理化及生物学特性的影响

Casper G. Schalkwijk , Mario A. Vermeer , Coen D.A. Stehouwer , Johan te Koppele , Hans M.G. Princen , Victor W.M. van Hinsbergh
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引用次数: 24

摘要

在糖尿病患者中,低密度脂蛋白(LDL)的非酶糖化已被认为参与动脉粥样硬化的发展。α-二羰基化合物被确定为非酶糖基化的中间体,并且在糖尿病患者中报告了其水平升高。我们研究了α-二羰基化合物甲基乙二醛(MG)对LDL理化和生物学特性的影响。MG剂量依赖性地修饰LDL,如荧光产物的形成和净负电荷的增加所示。MG (10 mmol/l)诱导了精氨酸残基的主要修饰(高达85%)和赖氨酸的次要修饰(少于6%)。通过细胞色素c的减少,MG-LDL制剂产生了少量的超氧阴离子自由基,但这并不伴随着MG-LDL的多不饱和脂肪酸的过氧化。MG-LDL在培养细胞中被人LDL受体识别和摄取减少,在大鼠体内血浆清除率显著增加。小鼠巨噬细胞对125i氧化LDL的关联降低和降解表明清除剂受体对MG-LDL的识别。令人惊讶的是,与天然LDL和氧化或乙酰化LDL相比,MG-LDL在小鼠巨噬细胞中引起的胆固醇酯合成明显减少。通过单核细胞趋化蛋白-1和血管细胞粘附分子-1的表达测量,高度修饰的MG-LDL不会诱导人内皮细胞的活化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effect of methylglyoxal on the physico-chemical and biological properties of low-density lipoprotein

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.

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