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糖基化晶状体蛋白在钙离子存在下的结构改变和聚集倾向:晶状体钙动态平衡在糖尿病性白内障发展中的重要性。

The structural alteration and aggregation propensity of glycated lens crystallins in the presence of calcium: Importance of lens calcium homeostasis in development of diabetic cataracts.

机构信息

Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.

Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.

出版信息

Spectrochim Acta A Mol Biomol Spectrosc. 2017 Jan 5;170:174-83. doi: 10.1016/j.saa.2016.07.017. Epub 2016 Jul 9.

Abstract

The imbalance of the calcium homeostasis in the lenticular tissues of diabetic patients is an important risk factor for development of cataract diseases. In the current study, the impact of elevated levels of calcium ions were investigated on structure and aggregation propensity of glycated lens crystallins using gel electrophoresis and spectroscopic assessments. The glycated proteins indicated significant resistance against calcium-induced structural insults and aggregation. While, glycated crystallins revealed an increased conformational stability; a slight instability was observed for these proteins upon interaction with calcium ions. Also, in the presence of calcium, the proteolytic pattern of native crystallins was altered and that of glycated protein counterparts remained almost unchanged. According to results of this study it is suggested that the structural alteration of lens crystallins upon glycation may significantly reduce their calcium buffering capacity in eye lenses. Therefore, under chronic hyperglycemia accumulation of this cataractogenic metal ion in the lenticular tissues may subsequently culminate in activation of different pathogenic pathways, leading to development of lens opacity and cataract diseases.

摘要

糖尿病患者晶状体组织中钙稳态失衡是白内障疾病发展的一个重要危险因素。在本研究中,使用凝胶电泳和光谱评估研究了钙离子水平升高对糖化晶状体蛋白结构和聚集倾向的影响。糖化蛋白对钙诱导的结构损伤和聚集具有显著的抗性。然而,糖化晶体蛋白显示出增加的构象稳定性;当这些蛋白质与钙离子相互作用时,观察到它们略有不稳定性。此外,在钙离子存在下,天然晶体蛋白的蛋白水解模式发生改变,而糖化蛋白对应物的蛋白水解模式几乎保持不变。根据本研究的结果,提示晶状体蛋白糖化后结构的改变可能会显著降低它们在眼晶状体中的钙缓冲能力。因此,在慢性高血糖症下,这种白内障形成金属离子在晶状体组织中的积累可能随后激活不同的致病途径,导致晶状体混浊和白内障疾病的发生。

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