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提取法和生物技术制备的硫酸软骨素对胰岛素淀粉样和糖基化终产物诱导的毒性的保护作用。

Protective effect of extractive and biotechnological chondroitin in insulin amyloid and advanced glycation end product-induced toxicity.

机构信息

Department of Precision Medicine, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.

Department of Experimental Medicine, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.

出版信息

J Cell Physiol. 2019 Apr;234(4):3814-3828. doi: 10.1002/jcp.27153. Epub 2018 Sep 7.

DOI:10.1002/jcp.27153
PMID:30256388
Abstract

Glycosaminoglycans are extracellular matrix components related to several biological functions and diseases. Chondroitin sulfate is a sulphated glycosaminoglycan synthesized as part of proteoglycan molecules. They are frequently associated with amyloid deposits and possess an active role in amyloid fibril formation. Recently, a neuroprotective effect of extracellular matrix components against amyloid toxicity and oxidative stress has been reported. Advanced glycation end products (AGEs), the end products of the glycation reaction, have been linked to amyloid-based neurodegenerative disease as associated with oxidative stress and inflammation. In this study we have analyzed the effect of chondroitin sulfate isolated from different species, in comparison with a new biotechnological unsulfated chondroitin, in the amyloid aggregation process of insulin, as well as the ability to prevent the formation of AGEs and related toxicity. The results have showed a determining role of chondroitin sulfate groups in modulating insulin amyloid aggregation. In addition, both sulfated and unsulfated chondroitins have shown protective properties against amyloid and AGEs-induced toxicity. These data are very relevant as a protective effect of these glycosaminoglycans in the AGE-induced toxicity was never observed before. Moreover, considering the issues related to the purity and safety of chondroitin from natural sources, this study suggests a new potential application for the biotechnological chondroitin.

摘要

糖胺聚糖是与多种生物学功能和疾病相关的细胞外基质成分。硫酸软骨素是一种合成的糖胺聚糖,是蛋白聚糖分子的一部分。它们经常与淀粉样沉积物有关,并在淀粉样纤维形成中具有积极作用。最近,有研究报道细胞外基质成分对淀粉样毒性和氧化应激具有神经保护作用。晚期糖基化终产物(AGEs)是糖基化反应的终产物,与淀粉样蛋白相关的神经退行性疾病有关,与氧化应激和炎症有关。在这项研究中,我们分析了从不同物种中分离的硫酸软骨素与新型生物技术非硫酸化软骨素在胰岛素淀粉样聚集过程中的作用,以及预防 AGEs 形成和相关毒性的能力。结果表明,硫酸软骨素基团在调节胰岛素淀粉样聚集中起着决定性作用。此外,硫酸化和非硫酸化软骨素都表现出对淀粉样和 AGEs 诱导的毒性的保护作用。这些数据非常重要,因为以前从未观察到这些糖胺聚糖对 AGE 诱导的毒性具有保护作用。此外,考虑到天然来源软骨素的纯度和安全性问题,本研究为生物技术软骨素提供了新的潜在应用。

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