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人低密度脂蛋白糖基化的研究:物理化学分析的功能洞察

Studies on glycation of human low density lipoprotein: a functional insight into physico-chemical analysis.

作者信息

Ahmad Saheem, Akhter Firoz, Shahab Uzma, Khan M Salman

机构信息

Clinical Biochemistry & Natural Product Research Lab, Department of Biosciences, Integral University, Lucknow 226026, India.

出版信息

Int J Biol Macromol. 2013 Nov;62:167-71. doi: 10.1016/j.ijbiomac.2013.08.037. Epub 2013 Sep 5.

DOI:10.1016/j.ijbiomac.2013.08.037
PMID:24012841
Abstract

Glycation of biomolecules leads to the establishment of advanced glycation end products (AGEs), which have significant role in the pathophysiology of diabetes leading to disorders, such as atherosclerosis. Ribose appears to be the most reactive among the naturally occurring sugars and contribute significantly to the glycation reactions in vivo, however, no report has been published to discuss D-ribose induced glycation of low density lipoprotein (LDL). The present study initially focuses on the glycation of commercially available LDL using different concentrations of D-ribose for varied incubation time intervals. The structural perturbations induced in LDL were analyzed by UV-vis, fluorescence & circular dichroism spectroscopy, and thermal denaturation studies. The ketoamine moieties, carbonyl content and HMF content were also quantitated in native and glycated LDL. We report structural perturbations, increased carbonyl content, ketoamine moieties and HMF content in D-ribose induced glycated LDL (LDL-AGEs) as compared to native analogue. These results provide evidence that LDL-AGEs could interfere in normal physiological functions and might contribute in the initiation of diabetes induced atherosclerosis and other secondary cardiovascular problems in diabetic patients. Though ours is a preliminary study, we are sure it would open the topic for further studies.

摘要

生物分子的糖基化会导致晚期糖基化终产物(AGEs)的形成,这些产物在糖尿病的病理生理过程中起着重要作用,可引发动脉粥样硬化等病症。核糖似乎是天然存在的糖类中反应活性最高的,在体内糖基化反应中起重要作用,然而,尚未有关于D -核糖诱导低密度脂蛋白(LDL)糖基化的报道。本研究最初聚焦于使用不同浓度的D -核糖在不同孵育时间间隔下对市售LDL进行糖基化。通过紫外可见光谱、荧光光谱和圆二色光谱以及热变性研究分析LDL中诱导的结构扰动。还对天然LDL和糖基化LDL中的酮胺基团、羰基含量和羟甲基糠醛(HMF)含量进行了定量。我们报告称,与天然LDL相比,D -核糖诱导的糖基化LDL(LDL - AGEs)存在结构扰动、羰基含量增加、酮胺基团和HMF含量增加。这些结果表明,LDL - AGEs可能会干扰正常生理功能,并可能在糖尿病患者糖尿病诱导的动脉粥样硬化及其他继发性心血管问题的发生中起作用。尽管我们的研究是初步的,但我们确信它将为进一步研究开启这个话题。

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