PMID- 20807286
OWN - NLM
STAT- MEDLINE
DCOM- 20120109
LR  - 20211020
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 15
IP  - 8
DP  - 2011 Aug
TI  - Butyrylcholinesterase interactions with amylin may protect pancreatic cells in 
      metabolic syndrome.
PG  - 1747-56
LID - 10.1111/j.1582-4934.2010.01165.x [doi]
AB  - The metabolic syndrome (MetS) is a risk factor for type 2 diabetes mellitus 
      (T2DM). However, the mechanisms underlying the transition from MetS to T2DM are 
      unknown. Our goal was to study the potential contribution of 
      butyrylcholinesterase (BChE) to this process. We first determined the hydrolytic 
      activity of BChE in serum from MetS, T2DM and healthy individuals. The 'Kalow' 
      variant of BChE (BChE-K), which has been proposed to be a risk factor for T2DM, 
      was genotyped in the last two groups. Our results show that in MetS patients 
      serum BChE activity is elevated compared to T2DM patients and healthy controls 
      (P < 0.001). The BChE-K genotype showed similar prevalence in T2DM and healthy 
      individuals, excluding this genotype as a risk factor for T2DM. However, the 
      activity differences remained unexplained. Previous results from our laboratory 
      have shown BChE to attenuate the formation of beta-amyloid fibrils, and protect 
      cultured neurons from their cytotoxicity. Therefore, we next studied the in vitro 
      interactions between recombinant human butyrylcholinesterase and amylin by 
      surface plasmon resonance, Thioflavine T fluorescence assay and cross-linking, 
      and used cultured pancreatic beta cells to test protection by BChE from amylin 
      cytotoxicity. We demonstrate that BChE interacts with amylin through its core 
      domain and efficiently attenuates both amylin fibril and oligomer formation. 
      Furthermore, application of BChE to cultured beta cells protects them from amylin 
      cytotoxicity. Taken together, our results suggest that MetS-associated BChE 
      increases could protect pancreatic beta-cells in vivo by decreasing the formation of 
      toxic amylin oligomers.
CI  - (c) 2011 The Authors Journal compilation (c) 2011 Foundation for Cellular and 
      Molecular Medicine/Blackwell Publishing Ltd.
FAU - Shenhar-Tsarfaty, Shani
AU  - Shenhar-Tsarfaty S
AD  - Department of Neurology and Internal Medicine, Tel Aviv Sourasky Medical Center, 
      Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Bruck, Tal
AU  - Bruck T
FAU - Bennett, Estelle R
AU  - Bennett ER
FAU - Bravman, Tsafrir
AU  - Bravman T
FAU - Aassayag, Einor Ben
AU  - Aassayag EB
FAU - Waiskopf, Nir
AU  - Waiskopf N
FAU - Rogowski, Ori
AU  - Rogowski O
FAU - Bornstein, Natan
AU  - Bornstein N
FAU - Berliner, Shlomo
AU  - Berliner S
FAU - Soreq, Hermona
AU  - Soreq H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.1.1.8 (Butyrylcholinesterase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Amino Acid Sequence
MH  - Butyrylcholinesterase/chemistry/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Diabetes Mellitus, Type 2/blood/genetics/metabolism
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Immunoblotting
MH  - Insulin-Secreting Cells/*metabolism
MH  - Islet Amyloid Polypeptide/chemistry/*metabolism/pharmacology
MH  - Male
MH  - Metabolic Syndrome/blood/genetics/*metabolism
MH  - Middle Aged
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Protein Multimerization
MH  - Recombinant Proteins/chemistry/metabolism/pharmacology
MH  - Surface Plasmon Resonance
PMC - PMC4373355
EDAT- 2010/09/03 06:00
MHDA- 2012/01/10 06:00
PMCR- 2011/08/01
CRDT- 2010/09/03 06:00
PHST- 2010/09/03 06:00 [entrez]
PHST- 2010/09/03 06:00 [pubmed]
PHST- 2012/01/10 06:00 [medline]
PHST- 2011/08/01 00:00 [pmc-release]
AID - JCMM1165 [pii]
AID - 10.1111/j.1582-4934.2010.01165.x [doi]
PST - ppublish
SO  - J Cell Mol Med. 2011 Aug;15(8):1747-56. doi: 10.1111/j.1582-4934.2010.01165.x.