Web of Science: 11 citas, Scopus: 11 citas, Google Scholar: citas,
Benzbromarone, Quercetin, and Folic Acid Inhibit Amylin Aggregation
López Rodríguez, Laura Catalina (Universidad de Zaragoza. Departamento de Bioquímica y Biología Molecular y Celular)
Varea, Olga (Universidad de Zaragoza. Departamento de Bioquímica y Biología Molecular y Celular)
Navarro Cantero, Susanna (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)
Carrodeguas Villar, José Alberto (Universidad de Zaragoza. Departamento de Bioquímica y Biología Molecular y Celular)
Sánchez de Groot, Natalia (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)
Ventura, Salvador (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)
Sancho Sanz, Javier (Universidad de Zaragoza. Departamento de Bioquímica y Biología Molecular y Celular)

Fecha: 2016
Resumen: Human Amylin, or islet amyloid polypeptide (hIAPP), is a small hormone secreted by pancreatic-cells that forms aggregates under insulin deficiency metabolic conditions, and it constitutes a pathological hallmark of type II diabetes mellitus. In type II diabetes patients, amylin is abnormally increased, self-assembled into amyloid aggregates, and ultimately contributes to the apoptotic death of -cells by mechanisms that are not completely understood. We have screened a library of approved drugs in order to identify inhibitors of amylin aggregation that could be used as tools to investigate the role of amylin aggregation in type II diabetes or as therapeutics in order to reduce -cell damage. Interestingly, three of the compounds analyzed—benzbromarone, quercetin, and folic acid—are able to slow down amylin fiber formation according to Thioflavin T binding, turbidimetry, and Transmission Electron Microscopy assays. In addition to the in vitro assays, we have tested the effect of these compounds in an amyloid toxicity cell culture model and we have found that one of them, quercetin, has the ability to partly protect cultured pancreatic insulinoma cells from the cytotoxic effect of amylin. Our data suggests that quercetin can contribute to reduce oxidative damage in pancreatic insulinoma cells by modulating the aggregation propensity of amylin.
Derechos: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Lengua: Anglès.
Documento: article ; recerca ; publishedVersion
Materia: Quercetina ; Benzbromarone ; Folic acid ; Amylin ; Amyloid ; Aggregation ; Type II diabetes
Publicado en: International Journal of Molecular Sciences, Vol. 17 Núm. 6 (june 2016) , ISSN 1422-0067

DOI: 10.3390/ijms17060964
PMID: 27322259


12 p, 2.1 MB

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