Blockade of islet amyloid polypeptide fibrillation and cytotoxicity by the secretory chaperones 7B2 and proSAAS.

• 影响指数: 3.864
• 发表时间: Nov 2013 1
• 来源期刊: FEBS Lett
• DOI: 10.1016/j.febslet.2013.09.006
• PMID: 24042052
• 文章类型: Journal Article
• 中科院分区: Q3
• 方向: 生物
• 作者列表: Peinado JR,Sami F,Rajpurohit N,Lindberg I

关键词: 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

Mesh: Animals; Cells, Cultured; Humans; Islet Amyloid Polypeptide / antagonists & inhibitors metabolism toxicity; Mice; Molecular Chaperones / metabolism; Nerve Tissue Proteins / metabolism; Neuroendocrine Secretory Protein 7B2 / metabolism; Neuropeptides; Rats

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.