Butyrylcholinesterase interactions with amylin may protect pancreatic cells in metabolic syndrome.
Bottom Line: However, the activity differences remained unexplained.We demonstrate that BChE interacts with amylin through its core domain and efficiently attenuates both amylin fibril and oligomer formation.Taken together, our results suggest that MetS-associated BChE increases could protect pancreatic β-cells in vivo by decreasing the formation of toxic amylin oligomers.
Affiliation: Department of Neurology and Internal Medicine, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.Show MeSH
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Mentions: ThT fluorescence signals reflect the amount of amyloid fibrils formed  but do not define their exact oligomeric state. To determine this, we used the PICUP method to cross-link amylin monomers, then separated the resulting oligomeric complexes by SDS-PAGE and visualized them by silver staining. As can be seen in Figure 5A, at the initial time-point (only 3–5 min. after mixing the reaction components) amylin attained several soluble forms, from monomers up to hexamers, reflecting its highly amyloidogeic nature. These soluble forms were not visible, however, at later time-points. When amylin was incubated in the presence of rhBChE it showed similar oligomeric forms at the initial time-point, but these remained in the soluble fraction for at least 12 hrs. In comparison, when amylin was incubated with LOX (Fig. 5B) the oligomeric forms disappeared from the soluble fraction by 6 hrs. Thus, rhBChE prolonged the persistence of small amylin oligomers in solution, whereas LOX accelerated their precipitation out of solution.
Affiliation: Department of Neurology and Internal Medicine, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.