Ascorbic acid inhibits human insulin aggregation and protects against amyloid induced cytotoxicity

被引：112

作者：

Alam, Parvez ^{[1
]}

Beg, Ayesha Zainab ^{[1
]}

Siddiqi, Mohammad Khursheed ^{[1
]}

Chaturvedi, Sunlit Kumar ^{[1
]}

Rajpoot, Ravi Kant ^{[2
]}

Ajmal, Mohd Rehan ^{[1
]}

Zaman, Masihuz ^{[1
]}

Abdelhameed, Ali S. ^{[3
]}

Khan, Rizwan Hasan ^{[1
]}

机构：

[1] Aligarh Muslim Univ, Interdisciplinary Biotechnol Unit, Mol Biophys & Biophys Chem Grp, Aligarh 202002, Uttar Pradesh, India

[2] Int Ctr Genet Engn & Biotechnol, Recombinant Gene Prod Grp, Aruna Asaf Ali Marg, New Delhi 110067, India

[3] King Saud Univ, Coll Pharm, Dept Pharmaceut Chem, Riyadh 11451, Saudi Arabia

来源：

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS | 2017年 / 621卷

关键词：

Amyloids; ThT binding; Beta sheet structure; Cell cytotoxicity; THIOFLAVIN-T; FIBRILS; BINDING; MECHANISM; INSIGHT;

D O I：

10.1016/j.abb.2017.04.005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Protein aggregation into oligomers and fibrils are associated with many human pathophysiologies. Compounds that modulate protein aggregation and interact with preformed fibrils and convert them to less toxic species, expect to serve as promising drug candidates and aid to the drug development efforts against aggregation diseases. In present study, the kinetics of amyloid fibril formation by human insulin (HI) and the anti-amyloidogenic activity of ascorbic acid (AA) were investigated by employing various spectroscopic, imaging and computational approaches. We demonstrate that ascorbic acid significantly inhibits the fibrillation of HI in a dose-dependent manner. Interestingly ascorbic acid destabilise the preformed amyloid fibrils and protects human neuroblastoma cell line (SH- SY5Y) against amyloid induced cytotoxicity. The present data signifies the role of ascorbic acid that can serve as potential molecule in preventing human insulin aggregation and associated pathophysiologies. (C) 2017 Elsevier Inc. All rights reserved.

引用

页码：54 / 62

页数：9

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