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Islet amyloid polypeptide-induced membrane leakage involves uptake of lipids by forming amyloid fibers

Sparr, Emma LU ; Engel, M F M; Sakharov, D V; Sprong, M; Jacobs, J; de Kruijff, B; Hoppener, J W M and Killian, J A (2004) In FEBS Letters 577(1-2). p.117-120
Abstract
Fibril formation of islet amyloid polypeptide (IAPP) is associated with cell death of the insulin-producing pancreatic beta-cells in patients with Type 2 Diabetes Mellitus. A likely cause for the cytotoxicity of human TAPP is that it destroys the barrier properties of the cell membrane. Here, we show by fluorescence confocal microscopy on lipid vesicles that the process of hIAPP amyloid formation is accompanied by a loss of barrier function, whereby lipids are extracted from the membrane and taken up in the forming amyloid deposits. No membrane interaction was observed when preformed fibrils were used. It is proposed that lipid uptake from the cell membrane is responsible for amyloid-induced membrane damage and that this represents a... (More)
Fibril formation of islet amyloid polypeptide (IAPP) is associated with cell death of the insulin-producing pancreatic beta-cells in patients with Type 2 Diabetes Mellitus. A likely cause for the cytotoxicity of human TAPP is that it destroys the barrier properties of the cell membrane. Here, we show by fluorescence confocal microscopy on lipid vesicles that the process of hIAPP amyloid formation is accompanied by a loss of barrier function, whereby lipids are extracted from the membrane and taken up in the forming amyloid deposits. No membrane interaction was observed when preformed fibrils were used. It is proposed that lipid uptake from the cell membrane is responsible for amyloid-induced membrane damage and that this represents a general mechanism underlying the cytotoxicity of amyloid forming proteins. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Amylin, Type II diabetes mellitus, Protein–membrane interaction, Amyloid, Model membrane
in
FEBS Letters
volume
577
issue
1-2
pages
117 - 120
publisher
Wiley-Blackwell
external identifiers
  • pmid:15527771
  • wos:000225128600020
  • scopus:7544245555
ISSN
1873-3468
DOI
10.1016/j.febslet.2004.09.075
language
English
LU publication?
yes
id
4520cf80-bc5a-4692-8523-1d178814858e (old id 154070)
date added to LUP
2007-07-12 11:55:12
date last changed
2017-12-10 04:25:18
@article{4520cf80-bc5a-4692-8523-1d178814858e,
  abstract     = {Fibril formation of islet amyloid polypeptide (IAPP) is associated with cell death of the insulin-producing pancreatic beta-cells in patients with Type 2 Diabetes Mellitus. A likely cause for the cytotoxicity of human TAPP is that it destroys the barrier properties of the cell membrane. Here, we show by fluorescence confocal microscopy on lipid vesicles that the process of hIAPP amyloid formation is accompanied by a loss of barrier function, whereby lipids are extracted from the membrane and taken up in the forming amyloid deposits. No membrane interaction was observed when preformed fibrils were used. It is proposed that lipid uptake from the cell membrane is responsible for amyloid-induced membrane damage and that this represents a general mechanism underlying the cytotoxicity of amyloid forming proteins. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.},
  author       = {Sparr, Emma and Engel, M F M and Sakharov, D V and Sprong, M and Jacobs, J and de Kruijff, B and Hoppener, J W M and Killian, J A},
  issn         = {1873-3468},
  keyword      = {Amylin,Type II diabetes mellitus,Protein–membrane interaction,Amyloid,Model membrane},
  language     = {eng},
  number       = {1-2},
  pages        = {117--120},
  publisher    = {Wiley-Blackwell},
  series       = {FEBS Letters},
  title        = {Islet amyloid polypeptide-induced membrane leakage involves uptake of lipids by forming amyloid fibers},
  url          = {http://dx.doi.org/10.1016/j.febslet.2004.09.075},
  volume       = {577},
  year         = {2004},
}