title: Blockade of islet amyloid polypeptide fibrillation and cytotoxicity by the secretory chaperones 7B2 and proSAAS.
abstract: The deposition of fibrillated human islet β-cell peptide islet amyloid polypeptide (hIAPP) into amyloid plaques is characteristic of the pathogenesis of islet cell death during type 2 diabetes. We investigated the effects of the neuroendocrine secretory proteins 7B2 and proSAAS on hIAPP fibrillation in vitro and on cytotoxicity. In vitro, 21-kDa 7B2 and proSAAS blocked hIAPP fibrillation. Structure-function studies showed that a central region within 21-kDa 7B2 is important in this effect and revealed the importance of the N-terminal region of proSAAS. Both chaperones blocked the cytotoxic effects of exogenous hIAPP on Rin5f cells; 7B2 generated by overexpression was also effective. ProSAAS and 7B2 may perform a chaperone role as secretory anti-aggregants in normal islet cell function and in type 2 diabetes.
authors.affiliation: Department of Anatomy and Neurobiology, University of Maryland-Baltimore, Baltimore, MD 21201, United States.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Peinado
authors.forename: Furqan
authors.initials: F
authors.lastname: Sami
authors.forename: Nina
authors.initials: N
authors.lastname: Rajpurohit
authors.forename: Iris
authors.initials: I
authors.lastname: Lindberg
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051859:Neuroendocrine Secretory Protein 7B2 / Q000378:metabolism*; D009479:Neuropeptides; D051381:Rats
chemical_list: D058228:Islet Amyloid Polypeptide; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D051859:Neuroendocrine Secretory Protein 7B2; D009479:Neuropeptides; C112832:Pcsk1n protein, mouse; C497678:SCG5 protein, human
keywords: 7B2; AD; Alzheimer’s disease; BSA; CA; FBS; IAPP; PBS; PC1/3; PD; Parkinson’s disease; T2DM; TBS; ThT; Type 2 diabetes; bovine serum albumin; carbonic anhydrase; fetal bovine serum; hIAPP; islet amyloid polypeptide; phosphate–buffered saline; proSAAS; prohormone convertase 1/3; thioflavin T; tris–buffered saline; type 2 diabetes
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