The amyloidogenic islet amyloid polypeptide (IAPP) and the associated pro-peptide ProIAPP(1-48) are involved in cell death in type 2 diabetes mellitus. It has been observed that interactions of this peptide with metal ions have an impact on the cytotoxicity of the peptides as well as on their deposition in the form of amyloid fibrils. In particular, Cu(II) seems to inhibit amyloid fibril formation, thus suggesting that Cu homeostasis imbalance may be involved in the pathogenesis of type 2 diabetes mellitus. We performed X-ray Absorption Spectroscopy (XAS) measurements of Cu(II)-ProIAPP complexes under near-physiological (10 mu M), equimolar concentrations of Cu(II) and peptide. Such low concentrations were made accessible to XAS measurements owing to the use of the High Energy Resolved Fluorescence Detection XAS facility recently installed at the ESRF beamline BM16 (FAME-UHD). Our preliminary data show that XAS measurements at micromolar concentrations are feasible and confirm that ProIAPP(1-48)-Cu(II) binding at near-physiological conditions can be detected.

De Santis, E., Shardlow, E., Stellato, F., Proux, O., Rossi, G., Exley, C., et al. (2019). X-Ray absorption spectroscopy measurements of Cu-ProIAPP complexes at physiological concentrations. CONDENSED MATTER, 4(1) [10.3390/condmat4010013].

X-Ray absorption spectroscopy measurements of Cu-ProIAPP complexes at physiological concentrations

De Santis, Emiliano;Stellato, Francesco
;
Rossi, Giancarlo;Morante, Silvia
2019-01-01

Abstract

The amyloidogenic islet amyloid polypeptide (IAPP) and the associated pro-peptide ProIAPP(1-48) are involved in cell death in type 2 diabetes mellitus. It has been observed that interactions of this peptide with metal ions have an impact on the cytotoxicity of the peptides as well as on their deposition in the form of amyloid fibrils. In particular, Cu(II) seems to inhibit amyloid fibril formation, thus suggesting that Cu homeostasis imbalance may be involved in the pathogenesis of type 2 diabetes mellitus. We performed X-ray Absorption Spectroscopy (XAS) measurements of Cu(II)-ProIAPP complexes under near-physiological (10 mu M), equimolar concentrations of Cu(II) and peptide. Such low concentrations were made accessible to XAS measurements owing to the use of the High Energy Resolved Fluorescence Detection XAS facility recently installed at the ESRF beamline BM16 (FAME-UHD). Our preliminary data show that XAS measurements at micromolar concentrations are feasible and confirm that ProIAPP(1-48)-Cu(II) binding at near-physiological conditions can be detected.
2019
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore FIS/07 - FISICA APPLICATA (A BENI CULTURALI, AMBIENTALI, BIOLOGIA E MEDICINA)
English
X-ray absorption spectroscopy; amylin; high energy resolution fluorescence detection
De Santis, E., Shardlow, E., Stellato, F., Proux, O., Rossi, G., Exley, C., et al. (2019). X-Ray absorption spectroscopy measurements of Cu-ProIAPP complexes at physiological concentrations. CONDENSED MATTER, 4(1) [10.3390/condmat4010013].
De Santis, E; Shardlow, E; Stellato, F; Proux, O; Rossi, G; Exley, C; Morante, S
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/236328
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