Sterol Structure Strongly Modulates Membrane-Islet Amyloid Polypeptide Interactions.
Biochemistry
; 57(12): 1868-1879, 2018 03 27.
Article
em En
| MEDLINE
| ID: mdl-29373018
ABSTRACT
Amyloid formation has been implicated in a wide range of human diseases, and the interaction of amyloidogenic proteins with membranes are believed to be important for many of them. In type-2 diabetes, human islet amyloid polypeptide (IAPP) forms amyloids, which contribute to ß-cell death and dysfunction in the disease. IAPP-membrane interactions are potential mechanisms of cytotoxicity. In vitro studies have shown that cholesterol significantly modulates the ability of model membranes to induce IAPP amyloid formation and IAPP-mediated membrane damage. It is not known if this is due to the general effects of cholesterol on membranes or because of specific sterol-IAPP interactions. The effects of replacing cholesterol with eight other sterols/steroids on IAPP binding to model membranes, membrane disruption, and membrane-mediated amyloid formation were examined. The primary effect of the sterols/steroids on the IAPP-membrane interactions was found to reflect their effect upon membrane order as judged by fluorescence anisotropy measurements. Specific IAPP-sterol/steroid interactions have smaller effects. The fraction of vesicles that bind IAPP was inversely correlated with the sterols/steroids' effect on membrane order, as was the extent of IAPP-induced membrane leakage and the time to form amyloids. The correlation between the fraction of vesicles binding IAPP and membrane leakage was particularly tight, suggesting the restriction of IAPP to a subset of vesicles is responsible for incomplete leakage.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Permeabilidade da Membrana Celular
/
Colesterol
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Polipeptídeo Amiloide das Ilhotas Pancreáticas
/
Membranas Artificiais
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article