Iwashima Y, Eto M, Hata A, Kaku K, Horiuchi S, Ushikubi F, Sano H
Department of Internal Medicine, Sano Hospital, Suehiro 3-3-1-15, Asahikawa, 078-8133, Japan.
Biochem Biophys Res Commun. 2000 Oct 22;277(2):368-80. doi: 10.1006/bbrc.2000.3685.
We investigated the effects of advanced glycation end products (AGEs) on the expression of oxidized low-density lipoprotein (OxLDL) receptors in human monocyte-derived macrophages and THP-1 cells treated with PMA. Both RT-PCR procedure and Northern blot analysis revealed that AGEs induced not only the gene expression of two major OxLDL receptors, macrophage scavenger receptor (MSR) class A and CD36, but also MSR-B I and lectin-like oxidized low-density lipoprotein receptor 1. Also, as a result of gel shift assay, AGEs increased transcriptional activities of AP-1, NF-kappaB, and peroxisome proliferator-activated receptor gamma. These findings indicate that AGEs-induced enhancement of these transcriptional activities might be involved in increased levels of mRNA for some of OxLDL receptors in THP-1-cells treated with PMA. The upregulated surface expression of these receptors on macrophage membranes was closely associated with increased uptake of modified LDL, and culminated in enhanced foam cell transformation. Thus, AGEs may be involved in the cause of variable levels of foam cell formation via the increased numbers of OxLDL receptors in accelerated atherosclerotic lesions of individuals with diabetes.
我们研究了晚期糖基化终末产物（AGEs）对经佛波酯（PMA）处理的人单核细胞衍生巨噬细胞和THP-1细胞中氧化型低密度脂蛋白（OxLDL）受体表达的影响。逆转录聚合酶链反应（RT-PCR）和Northern印迹分析均显示，AGEs不仅诱导了两种主要OxLDL受体，即A类巨噬细胞清道夫受体（MSR）和CD36的基因表达，还诱导了MSR-B I和凝集素样氧化型低密度脂蛋白受体1的基因表达。此外，凝胶迁移试验结果表明，AGEs增加了活化蛋白-1（AP-1）、核因子κB（NF-κB）和过氧化物酶体增殖物激活受体γ（PPARγ）的转录活性。这些发现表明，AGEs诱导的这些转录活性增强可能与PMA处理的THP-1细胞中某些OxLDL受体的mRNA水平升高有关。这些受体在巨噬细胞膜上上调的表面表达与修饰型低密度脂蛋白（LDL）摄取增加密切相关，并最终导致泡沫细胞转化增强。因此，在糖尿病患者加速的动脉粥样硬化病变中，AGEs可能通过增加OxLDL受体数量而参与不同程度的泡沫细胞形成。
