Dual effect of PEG-PE micelle over the oligomerization and fibrillation of human islet amyloid polypeptide

Xiaocui Fang; Maryam Yousaf; Qunxing Huang; Yanlian Yang; Chen Wang

doi:10.1038/s41598-018-22820-w

Dual effect of PEG-PE micelle over the oligomerization and fibrillation of human islet amyloid polypeptide

Sci Rep. 2018 Mar 13;8(1):4463. doi: 10.1038/s41598-018-22820-w.

Authors

Xiaocui Fang¹, Maryam Yousaf^{1

2}, Qunxing Huang¹, Yanlian Yang³, Chen Wang⁴

Affiliations

¹ CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, P. R. China.
² Radiation Chemistry Laboratory, Department of Chemistry, University of Agriculture, Faisalabad, 38000, Pakistan.
³ CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, P. R. China. yangyl@nanoctr.cn.
⁴ CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, P. R. China. wangch@nanoctr.cn.

Abstract

The oligomerization and fibrillation of human islet amyloid polypeptide (hIAPP) play a central role in the pathogenesis of type 2 diabetes. Strategies for remodelling the formation of hIAPP oligomers and fibrils have promising application potential in type 2 diabetes therapy. Herein, we demonstrated that PEG-PE micelle could inhibit hIAPP oligomerization and fibrillation through blocking the hydrophobic interaction and the conformational change from random coil to β-sheet structures of hIAPP. In addition, we also found that PEG-PE micelle could remodel the preformed hIAPP fibrils allowing the formation of short fibrils and co-aggregates. Taken together, PEG-PE micelle could rescue hIAPP-induced cytotoxicity by decreasing the content of hIAPP oligomers and fibrils that are related to the oxidative stress and cell membrane permeability. This study could be beneficial for the design and development of antiamyloidogenic agents.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line
Cell Survival / drug effects
Humans
Hydrophobic and Hydrophilic Interactions
Islet Amyloid Polypeptide / chemistry*
Micelles
Models, Molecular
Phosphatidylethanolamines / pharmacology*
Polyethylene Glycols / pharmacology*
Protein Aggregates / drug effects
Protein Multimerization / drug effects
Protein Structure, Secondary / drug effects

Substances

Islet Amyloid Polypeptide
Micelles
Phosphatidylethanolamines
Protein Aggregates
dioleoyl-N-(monomethoxypolyethylene glycol succinyl)phosphatidylethanolamine
Polyethylene Glycols