Antimicrobial activity of human islet amyloid polypeptides: an insight into amyloid peptides’ connection with antimicrobial peptides

2012 ◽  
Vol 393 (7) ◽  
pp. 641-646 ◽  
Author(s):  
Lan Wang ◽  
Qian Liu ◽  
Jin-Chun Chen ◽  
Yi-Xian Cui ◽  
Bing Zhou ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptides ◽  
Lipid Membrane ◽  
Human Islet ◽  
Amyloid Peptide ◽  
Islet Amyloid ◽  
Amyloid Peptides ◽  
Amyloid Polypeptides ◽  
New Evidence ◽  
Insight Into

Abstract Human islet amyloid polypeptide (hIAPP) shows an antimicrobial activity towards two types of clinically relevant bacteria. The potency of hIAPP varies with its aggregation states. Circular dichroism was employed to determine the interaction between hIAPP and bacteria lipid membrane mimic. The antimicrobial activity of each aggregate species is associated with their ability to induce membrane disruption. Our findings provide new evidence revealing the antimicrobial activity of amyloid peptide, which suggest a possible connection between amyloid peptides and antimicrobial peptides.

scholarly journals Rifampicin inhibits the toxicity of pre-aggregated amyloid peptides by binding to peptide fibrils and preventing amyloid-cell interaction

1997 ◽  
Vol 322 (3) ◽  
pp. 859-865 ◽  
Author(s):  
Takami TOMIYAMA ◽  
Hideshi KANEKO ◽  
Ken-ichiro KATAOKA ◽  
Satoshi ASANO ◽  
Noriaki ENDO
Keyword(s):  
Cell Surface ◽  
Immunofluorescence Microscopy ◽  
Therapeutic Potential ◽  
Cell Interaction ◽  
Human Islet ◽  
Surface Adhesion ◽  
Islet Amyloid ◽  
Amyloid Peptides ◽  
Pheochromocytoma Pc12 ◽  
Peptide Fibrils

Rifampicin and its analogues,p-benzoquinone and hydroquinone, inhibited the toxicity of preformed aggregates of human islet amyloid polypeptide, amylin, to rat pheochromocytoma PC12 cells, when preincubated with the aggregated peptide before addition to cell cultures. Immunofluorescence microscopy showed that they prevented the adhesion of amylin aggregates to the cell surface, and this effect was induced probably by their binding to peptide fibrils during preincubation. Other quinone derivatives, i.e., p-methoxyphenol, AA-861 and idebenone, failed to inhibit the toxicity and cell-surface adhesion of amylin aggregates. Rifampicin analogues also inhibited the toxicity of pre-aggregated amyloid β1–42 peptides, suggesting a common toxic mechanism of different amyloid peptides and their therapeutic potential for several amyloidoses.

scholarly journals Membrane Permeation Induced by Aggregates of Human Islet Amyloid Polypeptides

2013 ◽  
Vol 105 (10) ◽  
pp. 2323-2332 ◽  
Author(s):  
Chetan Poojari ◽  
Dequan Xiao ◽  
Victor S. Batista ◽  
Birgit Strodel
Keyword(s):  
Human Islet ◽  
Membrane Permeation ◽  
Islet Amyloid ◽  
Amyloid Polypeptides

scholarly journals Zinc Boosts EGCG’s hIAPP Amyloid Inhibition Both in Solution and Membrane

2018 ◽  
Author(s):  
Young-Ho Lee ◽  
Yuxi Lin ◽  
Sarah J. Cox ◽  
Misaki Kinoshita ◽  
Bikash R. Sahoo ◽  
...  
Keyword(s):  
Lipid Membrane ◽  
Islet Cells ◽  
Epigallocatechin Gallate ◽  
Helical Structure ◽  
Amyloid Peptide ◽  
Amyloid Aggregation ◽  
Islet Amyloid ◽  
Cellular Toxicity ◽  
Transmission Electron ◽  
Amyloid Diseases

AbstractAmyloid aggregation of human islet amyloid polypeptide (hIAPP) is linked to insulin-producing islet cell death in type II diabetes. Previous studies have shown the amyloid inhibiting effects of zinc (Zn) and insulin that are co-present with hIAPP in islet cells, and the lipid membrane has been shown to significantly influence the aggregation kinetics. Increasing number of studies report the importance of developing small molecule inhibitors to suppress the hIAPP’s toxicity. Particularly, the ability of epigallocatechin-gallate (EGCG) to inhibit amyloid aggregation of a variety of amyloid peptide/proteins including hIAPP initiated numerous studies including the development of compounds to potentially treat amyloid diseases. In this study, by using a combination of thioflavin-T fluorescence and transmission electron microscopy experiments, we demonstrate a significant enhancement in EGCG’s efficiency, when mixed with Zn, to significantly suppress hIAPP amyloid aggregation both in presence and absence of lipid membrane. Circular dichroism experiments indicate the formation and stabilization of a helical structure of hIAPP in presence of EGCG:Zn complex. Our results also reveal the ability of EGCG or EGCG:Zn to suppress hIAPP’s cellular toxicity and that the ability of EGCG to chelate with Zn suppresses zinc’s cellular toxicity. We suggest that the reported results would be useful to develop strategies to trap hIAPP intermediates for further biophysical and structural studies, and also to devise approaches to abolish amyloid aggregation and cellular toxicity.

Enhanced optical asymmetry in supramolecular chiroplasmonic assemblies with long-range order

Science ◽  
2021 ◽  
Vol 371 (6536) ◽  
pp. 1368-1374 ◽  
Author(s):  
Jun Lu ◽  
Yao Xue ◽  
Kalil Bernardino ◽  
Ning-Ning Zhang ◽  
Weverson R. Gomes ◽  
...  
Keyword(s):  
Long Range ◽  
Gold Nanorods ◽  
Spectral Shift ◽  
Human Islet ◽  
Range Order ◽  
Long Range Order ◽  
Islet Amyloid ◽  
Strong Polarization ◽  
Amyloid Polypeptides ◽  
Strong Scattering

Chiral assemblies of plasmonic nanoparticles are known for strong circular dichroism but not for high optical asymmetry, which is limited by the unfavorable combination of electrical and magnetic field components compounded by strong scattering. Here, we show that these limitations can be overcome by the long-range organization of nanoparticles in a manner similar to the liquid crystals and found in helical assemblies of gold nanorods with human islet amyloid polypeptides. A strong, polarization-dependent spectral shift and the reduced scattering of energy states with antiparallel orientation of dipoles activated in assembled helices increased optical asymmetry g-factors by a factor of more than 4600. The liquid crystal–like color variations and the nanorod-accelerated fibrillation enable drug screening in complex biological media. Improvement of long-range order can also provide structural guidance for the design of materials with high optical asymmetry.

Cu(II) cyclen cleavage agent for human islet amyloid peptide

2010 ◽  
Vol 18 (7) ◽  
pp. 2598-2601 ◽  
Author(s):  
Keunhong Jeong ◽  
Woo Young Chung ◽  
Young-Sik Kye ◽  
Dongwook Kim
Keyword(s):  
Human Islet ◽  
Amyloid Peptide ◽  
Islet Amyloid

Glycated Insulin Exacerbates the Cytotoxicity of Human Islet Amyloid Polypeptides: a Vicious Cycle in Type 2 Diabetes

2019 ◽  
Vol 14 (3) ◽  
pp. 486-496 ◽  
Author(s):  
Liang Ma ◽  
Chen Yang ◽  
Lianqi Huang ◽  
Yuchen Chen ◽  
Yang Li ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Human Islet ◽  
Vicious Cycle ◽  
Islet Amyloid ◽  
Amyloid Polypeptides

scholarly journals The small molecule inhibitor anle145c thermodynamically traps human islet amyloid peptide in the form of non-cytotoxic oligomers

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Manikam S. Saravanan ◽  
Sergey Ryazanov ◽  
Andrei Leonov ◽  
Janine Nicolai ◽  
Patrique Praest ◽  
...  
Keyword(s):  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Human Islet ◽  
Amyloid Peptide ◽  
Amyloid Formation ◽  
Islet Amyloid ◽  
Efficient Manner ◽  
Aggregation State ◽  
Molecule Inhibitor

AbstractType 2 diabetes (T2DM) is associated with aggregation of the human islet amyloid polypeptide (hIAPP) into cytotoxic amyloid species. Here we tested the effect of a diphenylpyrazole (DPP)-derived small molecule inhibitor, anle145c, on cytotoxicity and on aggregation properties of hIAPP. We demonstrate that incubation of hIAPP with the inhibitor yields ~10 nm-sized non-toxic oligomers, independent of the initial aggregation state of hIAPP. This suggests that anle145c has a special mode of action in which anle145c-stabilized oligomers act as a thermodynamic sink for the preferred aggregation state of hIAPP and anle145c. We also demonstrate that the inhibitor acts in a very efficient manner, with sub-stoichiometric concentrations of anle145c being sufficient to (i) inhibit hIAPP-induced death of INS-1E cells, (ii) prevent hIAPP fibril formation in solution, and (iii) convert preformed hIAPP fibrils into non-toxic oligomers. Together, these results indicate that anle145c is a promising candidate for inhibition of amyloid formation in T2DM.

Computational insights into the inhibition and destabilization of morin on the oligomer of full-length human islet amyloid polypeptide

2015 ◽  
Vol 17 (43) ◽  
pp. 29103-29112 ◽  
Author(s):  
Qianqian Wang ◽  
Shuangyan Zhou ◽  
Wei Wei ◽  
Xiaojun Yao ◽  
Huanxiang Liu ◽  
...  
Keyword(s):  
Binding Sites ◽  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Full Length ◽  
Amyloid Peptide ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide ◽  
Mechanism Of Inhibition

In this work, we simulated the full-length human islet amyloid peptide (hIAPP) pentamer with and without morins to investigate the mechanism of inhibition and destabilization of this inhibitor on hIAPP oligomer, and identify its possible binding sites on hIAPP.

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