IIRC-1, Laboratory of Glycation Biology and Metabolic Disorders, Integral University, Lucknow, India; Department of Biosciences, Integral University, Lucknow, India.
Department of Clinical Laboratory Sciences, University of Hail, Kingdom of Saudi Arabia.
Int J Biol Macromol. 2018 Aug;115:287-299. doi: 10.1016/j.ijbiomac.2018.04.016. Epub 2018 Apr 7.
Glycation initiates with the non-enzymatic reaction of amino group of proteins and lipoproteins by carbonyl group of sugar moiety and intermediates of glycative stress such as methylglyoxal (MG). The initial glycation leads to the formation of early glycation products (Amadori products) which undergo rearrangement, cyclization and dehydration to form advanced glycation end products (AGEs). The main objective of the present study is to investigate the non-enzymatic glycation of low density lipoprotein (LDL) by MG at different concentration and at increasing incubation time period in vitro. This modification may increase the formation of Amadori products and AGEs which are physico-chemically characterized with respect to the extent of LDL modification. Additionally, immunogenicity of native and MG modified LDL (MG-LDL) was probed in female rabbits in vivo. Immunogenicity of MG-LDL was found to be highly immunogenic, eliciting high titer immunogen-specific antibodies while native form of LDL is less immunogenic. Furthermore, the histopathology and immune-fluorescence studies suggest that the kidney section of immunized rabbits exhibit the presence of immune complex (MG-LDL-IgG) deposition in the glomerular basement membrane (GBM).
糖基化作用始于蛋白质和脂蛋白的氨基与糖部分的羰基以及糖基化应激的中间产物如甲基乙二醛（MG）的非酶反应。初始糖基化导致早期糖基化产物（Amadori 产物）的形成，其经历重排、环化和脱水以形成晚期糖基化终产物（AGEs）。本研究的主要目的是研究不同浓度的 MG 在体外对低密度脂蛋白（LDL）的非酶糖化作用，并在延长孵育时间的情况下进行。这种修饰可能会增加 Amadori 产物和 AGEs 的形成，这些产物在 LDL 修饰的程度方面具有物理化学特征。此外，还在体内雌性兔中探测天然和 MG 修饰的 LDL（MG-LDL）的免疫原性。发现 MG-LDL 的免疫原性非常高，可引发高滴度的免疫原特异性抗体，而天然形式的 LDL 的免疫原性较低。此外，组织病理学和免疫荧光研究表明，免疫兔的肾脏切片在肾小球基底膜（GBM）中存在免疫复合物（MG-LDL-IgG）沉积。
