title: Influence of Aluminium and EGCG on Fibrillation and Aggregation of Human Islet Amyloid Polypeptide.
abstract: The abnormal fibrillation of human islet amyloid polypeptide (hIAPP) has been implicated in the development of type II diabetes. Aluminum is known to trigger the structural transformation of many amyloid proteins and induce the formation of toxic aggregate species. The (-)-epigallocatechin gallate (EGCG) is considered capable of binding both metal ions and amyloid proteins with inhibitory effect on the fibrillation of amyloid proteins. However, the effect of Al(III)/EGCG complex on hIAPP fibrillation is unclear. In the present work, we sought to view insight into the structures and properties of Al(III) and EGCG complex by using spectroscopic experiments and quantum chemical calculations and also investigated the influence of Al(III) and EGCG on hIAPP fibrillation and aggregation as well as their combined interference on this process. Our studies demonstrated that Al(III) could promote fibrillation and aggregation of hIAPP, while EGCG could inhibit the fibrillation of hIAPP and lead to the formation of hIAPP amorphous aggregates instead of the ordered fibrils. Furthermore, we proved that the Al(III)/EGCG complex in molar ratio of 1 : 1 as Al(EGCG)(H2O)2could inhibit the hIAPP fibrillation more effectively than EGCG alone. The results provide the invaluable reference for the new drug development to treat type II diabetes.
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China.
authors.forename: Zhi-Xue
authors.initials: ZX
authors.lastname: Xu
authors.affiliation: Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Collaborative Innovation Center of Chemistry for Energy Material, Shanghai Key Laboratory of Molecular Catalysis & Innovative Materials, Department of Chemistry, Fudan University, Shanghai 200433, China.
authors.forename: Gong-Li
authors.initials: GL
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China.
authors.forename: Cong-Heng
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
authors.forename: Yan-Ming
authors.initials: YM
authors.lastname: He
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China.
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Xu
authors.affiliation: Department of Medicine, St Vincent's Hospital, The University of Melbourne, Fitzroy, VIC 3065, Australia.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China.
authors.forename: Guang-Rong
authors.initials: GR
authors.lastname: Zhou
authors.affiliation: Collaborative Innovation Center of Chemistry for Energy Material, Shanghai Key Laboratory of Molecular Catalysis & Innovative Materials, Department of Chemistry, Fudan University, Shanghai 200433, China.
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Li
authors.affiliation: Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
authors.forename: Hong-Jie
authors.identifier: 0000-0002-8054-9313
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China.
authors.forename: Ping
authors.identifier: 0000-0002-5954-7655
authors.initials: P
authors.lastname: Zhou
mesh_terms: D000535:Aluminum / Q000627:therapeutic use*; D000682:Amyloid / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002614:Chelating Agents / Q000737:chemistry; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000378:metabolism*; D007700:Kinetics; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D046529:Microscopy, Electron, Transmission; D012542:Scattering, Radiation; D013050:Spectrometry, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000682:Amyloid; D002614:Chelating Agents; D058228:Islet Amyloid Polypeptide; D002392:Catechin; C045651:epigallocatechin gallate; D000535:Aluminum