PMID- 25495656
OWN - NLM
STAT- MEDLINE
DCOM- 20150827
LR  - 20141224
IS  - 1464-5203 (Electronic)
IS  - 0968-7688 (Linking)
VI  - 31
IP  - 7-8
DP  - 2014 Nov-Dec
TI  - Cholesterol modulates the interaction of the islet amyloid polypeptide with 
      membranes.
PG  - 239-49
LID - 10.3109/09687688.2014.987182 [doi]
AB  - The deposition of insoluble amyloid fibrils resulting from the aggregation of the 
      human islet amyloid polypeptide (hIAPP) within the islet of Langerhans is a 
      pathological feature of type 2 diabetes mellitus (T2DM). Increasing evidence 
      indicates that biological membranes play a key role in amyloid aggregation, 
      modulating among others the kinetics of amyloid formation, and being the target 
      of toxic species generated during amyloid formation. In T2DM patients, elevated 
      levels of cholesterol, an important determinant of the physical state of 
      biological membranes, are observed in beta-cells and are thought to directly impair 
      beta-cell function and insulin secretion. However, it is not known whether 
      cholesterol enhances membrane-interaction or membrane-insertion of hIAPP. In this 
      study, we investigated the effect of cholesterol incorporated in zwitterionic and 
      anionic membranes. Our circular dichroism and liquid state NMR data reveal that 
      10-30% of cholesterol slightly affects the aggregational and conformational 
      behaviour of hIAPP. Additional fluorescence results indicate that 10 and 20% of 
      cholesterol slightly slow down the kinetics of oligomer and fibril formation 
      while anionic lipids accelerate this kinetics. This behavior might be caused by 
      differences in membrane insertion and therefore in membrane binding of hIAPP. The 
      membrane binding affinity was evaluated using (1)H NMR experiments and our 
      results show that the affinity of hIAPP for membranes containing cholesterol is 
      significantly smaller than that for membranes containing anionic lipids. 
      Furthermore, we found that hIAPP-induced membrane damage is synchronized to 
      fibril formation in the absence and in the presence of cholesterol.
FAU - Caillon, Lucie
AU  - Caillon L
AD  - Sorbonne Universites , UPMC Univ Paris 06, Laboratoire des Biomolecules , Paris, 
      France .
FAU - Duma, Luminita
AU  - Duma L
FAU - Lequin, Olivier
AU  - Lequin O
FAU - Khemtemourian, Lucie
AU  - Khemtemourian L
LA  - eng
PT  - Journal Article
DEP - 20141215
PL  - England
TA  - Mol Membr Biol
JT  - Molecular membrane biology
JID - 9430797
RN  - 0 (Anions)
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 0 (Membrane Lipids)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Anions/metabolism
MH  - Cell Membrane/*chemistry/metabolism
MH  - Cholesterol/*metabolism
MH  - Circular Dichroism
MH  - Diabetes Mellitus, Type 2/metabolism
MH  - Humans
MH  - Insulin-Secreting Cells/metabolism
MH  - Islet Amyloid Polypeptide/*chemistry/*metabolism
MH  - Membrane Lipids/metabolism
MH  - Protein Conformation
MH  - Proton Magnetic Resonance Spectroscopy
OTO - NOTNLM
OT  - Amyloid
OT  - cholesterol
OT  - peptide-membrane interactions
EDAT- 2014/12/17 06:00
MHDA- 2015/08/28 06:00
CRDT- 2014/12/16 06:00
PHST- 2014/12/16 06:00 [entrez]
PHST- 2014/12/17 06:00 [pubmed]
PHST- 2015/08/28 06:00 [medline]
AID - 10.3109/09687688.2014.987182 [doi]
PST - ppublish
SO  - Mol Membr Biol. 2014 Nov-Dec;31(7-8):239-49. doi: 10.3109/09687688.2014.987182. 
      Epub 2014 Dec 15.