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一项免疫组织化学分析,以验证D-核糖基化低密度脂蛋白免疫原性增强背后的原理。

An immunohistochemical analysis to validate the rationale behind the enhanced immunogenicity of D-ribosylated low density lipo-protein.

作者信息

Akhter Firoz, Khan M Salman, Singh Sarika, Ahmad Saheem

机构信息

Department of Bio-Engineering, Integral University, Lucknow, India; Department of Bio-Sciences, Integral University, Lucknow, India.

Department of Bio-Sciences, Integral University, Lucknow, India.

出版信息

PLoS One. 2014 Nov 13;9(11):e113144. doi: 10.1371/journal.pone.0113144. eCollection 2014.

Abstract

Advanced glycation end products (AGEs) are thought to contribute to the abnormal lipoprotein profiles and increased risk of cardiovascular disease in patients with diabetes and renal failure. D-ribose is one of the naturally occurring pentose monosaccharide present in all living cells and is a key component of numerous biomolecules involved in many important metabolic pathways. Formation of D-ribose derived glycated low density lipoprotein (LDL) has been previously demonstrated but no studies have been performed to assess the immune complex deposition in the kidney of rabbits immunized with glycated LDL. In this study, LDL was glycated with D-ribose, and it was further used as an immunogen for immunizing NZW female rabbits. The results showed that female rabbits immunized with D-ribose modified LDL induced antibodies as detected by direct binding and competitive ELISA. The modified LDL was found to be highly immunogenic eliciting high titer immunogen-specific antibodies, while the native forms were moderately immunogenic. The induced antibodies from modified LDL exhibited wide range of heterogeneity in recognizing various proteins and amino acids conformers. Furthermore, our histopathological results illustrated the deposits of immune complex in glomerular basement membrane in rabbits immunized with D-ribose-LDL.

摘要

晚期糖基化终末产物(AGEs)被认为与糖尿病和肾衰竭患者异常的脂蛋白谱以及心血管疾病风险增加有关。D-核糖是所有活细胞中天然存在的戊糖单糖之一,是许多参与重要代谢途径的生物分子的关键组成部分。此前已证实会形成D-核糖衍生的糖化低密度脂蛋白(LDL),但尚未开展研究评估用糖化LDL免疫的兔子肾脏中的免疫复合物沉积情况。在本研究中,LDL与D-核糖进行糖基化反应,然后将其用作免疫原免疫新西兰白兔雌性。结果显示,通过直接结合和竞争性酶联免疫吸附测定法检测到,用D-核糖修饰的LDL免疫的雌性兔子诱导产生了抗体。发现修饰后的LDL具有高度免疫原性,可引发高滴度的免疫原特异性抗体,而天然形式的免疫原性中等。修饰后的LDL诱导产生的抗体在识别各种蛋白质和氨基酸构象时表现出广泛的异质性。此外,我们的组织病理学结果表明,用D-核糖-LDL免疫的兔子肾小球基底膜中有免疫复合物沉积。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6ba/4231124/67025c19423f/pone.0113144.g001.jpg

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