Blockade of islet amyloid polypeptide fibrillation and cytotoxicity by the secretory chaperones 7B2 and proSAAS. Issue 21 (13th September 2013)

• Record Type: Journal Article
• Authors: Peinado, Juan R.; Sami, Furqan; Rajpurohit, Nina; Lindberg, Iris
• Is Part Of: FEBS letters. Volume 587:Issue 21(2013)
• Page Start: 3406
• Page End: 3411
• Publication Date: 2013-09-13
• Subjects: T2DM -- type 2 diabetes -- AD -- Alzheimer's disease -- PD -- Parkinson's disease -- PC1/3 -- prohormone convertase 1/3 -- PBS -- phosphate–buffered saline -- BSA -- bovine serum albumin -- TBS -- tris–buffered saline -- ThT -- thioflavin T -- FBS -- fetal bovine serum -- IAPP -- islet amyloid polypeptide -- CA -- carbonic anhydrase -- Type 2 diabetes -- hIAPP -- 7B2 -- proSAAS; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2013.09.006
• Languages: English
• ISSNs: 0014-5793

Abstract

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. Abstract : 21‐kDa 7B2 and proSAAS blocked hIAPP fibrillation in vitro. The central region within 21‐kDa 7B2 is important for the inhibition of hIAPP fibrillation. The N‐terminal region of proSAAS is important for the inhibition of hIAPP fibrillation. Both chaperones blocked the cytotoxic effects of exogenous hIAPP on Rin5f cells when added exogenously. Overexpressed 7B2 also blocked the cytotoxic effects of exogenous hIAPP.