title: Molecular and cytotoxic properties of hIAPP17-29 and rIAPP17-29 fragments: a comparative study with the respective full-length parent polypeptides.
abstract: The human islet polypeptide (hIAPP) or amylin is a 37-residue peptide hormone secreted by β-cells of the islet of Langerhans in the pancreas. Unlike the rat variant of IAPP (rIAPP), human amylin is highly amyloidogenic and is found as amyloid deposits in nearly 95% of patients afflicted with type 2 diabetes mellitus (T2DM). Human and rat IAPP have nearly identical primary sequence differing at only six positions which are encompassed within the 17-29 aminoacid region. Using Circular Dichroism (CD), Dynamic Light Scattering (DLS) and ThT-fluorescence (Th-T), we examined the aggregation properties of both full-length hIAPP1-37 and the related peptide fragment hIAPP17-29. For the sake of comparison, similar experiments were carried out on the respective rat variants rIAPP1-37 and rIAPP17-29. These studies were conducted at physiological pH in buffered solution not containing fluorinated co-solvents as well as in the presence of model membranes (LUV). In addition, the cytotoxic activity of the investigated peptides was determined toward different pancreatic β-cell lines. All the peptide studied in this work resulted cytotoxic despite β-sheet structure being observed, in vitro, for the hIAPP1-37 only. This suggests that β-sheet conformational transition that generally precedes the fibril formation, is not a prerequisite for toxicity towards β-cells. Interestingly, confocal microscopy indicated that the IAPP peptides can enter the cell and might exert their toxic action at an intracellular level.
authors.affiliation: CNR-Institute of Biostructures and Bioimaging, Via P. Gaifami 18, 95126 Catania, Italy.
authors.forename: Marianna Flora
authors.initials: MF
authors.lastname: Tomasello
authors.affiliation: International PhD Program in Translational Biomedicine, University of Catania, V.le A. Doria 6, 95125 Catania, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sinopoli
authors.affiliation: CNR-Institute of Biostructures and Bioimaging, Via P. Gaifami 18, 95126 Catania, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Attanasio
authors.affiliation: CNR-Institute of Biostructures and Bioimaging, Via P. Gaifami 18, 95126 Catania, Italy.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Giuffrida
authors.affiliation: CNR-Institute of Biostructures and Bioimaging, Via P. Gaifami 18, 95126 Catania, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Campagna
authors.affiliation: CNR-Institute of Biostructures and Bioimaging, Via P. Gaifami 18, 95126 Catania, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Milardi
authors.affiliation: CNR-Institute of Biostructures and Bioimaging, Via P. Gaifami 18, 95126 Catania, Italy. Electronic address: giuseppe.pappalardo@cnr.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pappalardo
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D051381:Rats; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments
keywords: Amyloid; Confocal microscopy; Mitochondria; Model membranes; Spectroscopy; Type 2 diabetes