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暴露于过氧自由基的人低密度脂蛋白中的蛋白质氧化促进单核细胞摄取;抗氧化剂在体外具有保护作用。

Oxidation of protein in human low-density lipoprotein exposed to peroxyl radicals facilitates uptake by monocytes; protection by antioxidants in vitro.

机构信息

Molecular Biosciences, Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.

出版信息

Environ Toxicol Pharmacol. 2004 Jan;15(2-3):111-7. doi: 10.1016/j.etap.2003.11.006.

DOI:10.1016/j.etap.2003.11.006
PMID:21782687
Abstract

Generation of neoepitopes on apolipoprotein B within oxidised low-density lipoprotein (LDL) is important in the unregulated uptake of LDL by monocytic scavenger receptors (CD36, SR-AI, LOX-1). Freshly isolated LDL was oxidised by peroxyl radicals generated from the thermal decomposition of an aqueous azo-compound. We describe that formation of carbonyl groups on the protein component is early as protein oxidation was seen after 90min. This is associated with an increased propensity for LDL uptake by U937 monocytes. Three classes of antioxidants (quercetin, dehydroepiandrosterone (DHEA) and ascorbic acid) have been examined for their capacity to inhibit AAPH-induced protein oxidation, (protein carbonyls, Δ electrophoretic mobility and LDL uptake by U937 monocytes). CD36 expression was assessed by flow cytometry and was seen to be unaltered by oxidised LDL uptake. All three classes were effective antioxidants, quercetin (P<0.01), ascorbic acid (P<0.01), DHEA (P<0.05). As LDL protein is the control point for LDL metabolism, the degree of oxidation and protection by antioxidants is likely to be of great importance for (patho)-physiological uptake of LDL by monocytes.

摘要

在氧化型低密度脂蛋白(LDL)中载脂蛋白 B 上新表位的产生对于单核细胞清道夫受体(CD36、SR-AI、LOX-1)对 LDL 的非调节性摄取非常重要。新鲜分离的 LDL 通过水相中偶氮化合物热分解产生的过氧自由基氧化。我们描述了蛋白质成分上羰基的形成很早就发生了,因为在 90 分钟后就观察到了蛋白质氧化。这与 U937 单核细胞对 LDL 摄取的增加倾向有关。三种类别的抗氧化剂(槲皮素、脱氢表雄酮(DHEA)和抗坏血酸)已被用于研究其抑制 AAPH 诱导的蛋白质氧化(蛋白质羰基、Δ电泳迁移率和 U937 单核细胞摄取 LDL)的能力。通过流式细胞术评估 CD36 的表达,发现其不受氧化型 LDL 摄取的影响。所有三类都是有效的抗氧化剂,槲皮素(P<0.01)、抗坏血酸(P<0.01)、DHEA(P<0.05)。由于 LDL 蛋白是 LDL 代谢的控制点,因此氧化程度和抗氧化剂的保护作用对于单核细胞对 LDL 的(病理)生理摄取可能非常重要。

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