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Protein aggregation as a consequence of non-enzymatic glycation: Therapeutic intervention using aspartic acid and arginine.
International Journal of Biological Macromolecules ( IF 8.2 ) Pub Date : 2020-09-19 , DOI: 10.1016/j.ijbiomac.2020.09.083
Anna Feroz 1 , Peerzada Shariq Shaheen Khaki 2 , Mohd Sajid Khan 1 , Bilqees Bano 2
Affiliation  

Non-enzymatic glycation tempted AGEs of proteins are currently at the heart of a number of pathological conditions. Production of chemically stable AGEs can permanently alter the protein structure and function, concomitantly leading to dilapidated situations. Keeping in perspective, present study aims to report the glycation induced structural and functional modification of a cystatin type isolated from rai mustard seeds, using RSC-glucose and RSC-ribose as model system. Among the sugars studied, ribose was found to be most potent glycating agent as evident from different biophysical assays. During the course of incubation, RSC was observed to pass through a series of structural intermediates as revealed by circular dichroism, altered intrinsic fluorescence and high ANS binding. RSC incubation with ribose post day 36 revealed the possible buildup of β structures as observed in CD spectral analysis, hinting towards the generation of aggregated structures in RSC. High thioflavin T fluorescence and increased Congo red absorbance together with enhanced turbidity of the modified form confirmed the aggregation of RSC. The study further revealed anti-glycation and anti-aggregation potential of amino acids; aspartic acid and arginine as they prevented and/or slowed down the process of AGEs and β structure buildup in a concentration dependent manner with arginine proving to be the most effective one.



中文翻译:

非酶糖基化导致的蛋白质聚集:使用天冬氨酸和精氨酸的治疗干预。

蛋白质的非酶促糖基化AGEs目前是许多病理状况的核心。化学上稳定的AGEs的产生会永久性地改变蛋白质的结构和功能,从而导致残旧的情况。保持眼光,本研究旨在报告糖化诱导的芥菜籽分离的半胱氨酸蛋白酶抑制剂类型的结构和功能修饰,使用RSC-葡萄糖和RSC-核糖作为模型系统。从不同的生物物理分析中可以明显看出,在所研究的糖中,核糖是最有效的糖化剂。在孵育过程中,观察到RSC穿过一系列结构中间体,这通过圆二色性,改变的固有荧光和高ANS结合表现出来。第36天后,用核糖进行RSC孵育后发现CD结构分析中观察到的β结构可能堆积,这暗示了RSC中聚集结构的产生。高硫黄素T荧光和增加的刚果红吸光度以及修饰形式的浊度提高证实了RSC的聚集。该研究进一步揭示了氨基酸的抗糖化和抗聚集的潜力。天冬氨酸和精氨酸,它们以浓度依赖的方式预防和/或减缓了AGEs和β结构的建立,精氨酸被证明是最有效的。高硫黄素T荧光和增加的刚果红吸光度以及修饰形式的浊度提高证实了RSC的聚集。该研究进一步揭示了氨基酸的抗糖化和抗聚集的潜力。天冬氨酸和精氨酸,它们以浓度依赖的方式预防和/或减缓了AGEs和β结构的建立,精氨酸被证明是最有效的。高硫黄素T荧光和增加的刚果红吸光度以及修饰形式的浊度提高证实了RSC的聚集。该研究进一步揭示了氨基酸的抗糖化和抗聚集的潜力。天冬氨酸和精氨酸,它们以浓度依赖的方式预防和/或减缓了AGEs和β结构的建立,精氨酸被证明是最有效的。

更新日期:2020-09-20
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