XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Posters
88.
PHYTOALEXINS REDUCE INSULIN AMYLOID AGGREGATION
Katarína Šipošová 1 , Andrea Antošová 2 , Peter Kutschy 1 ,
Zuzana Daxnerová 3 and Zuzana Gažová 2
1
Institute of Chemical Sciences, 3 Institute of Biology and Ecology, Faculty of Science,
P. J. Šafárik University, Košice, Slovakia, 2 Department of Biophysics, Institute of
Experimental Physics SAS, Košice, Slovakia
Amyloid aggregation, a generic behavior of proteins, is related to incurable human pathologies
(amyloid-related diseases) associated with formation of amyloid deposits in
the body. Insulin amyloid deposits have been observed in patients with diabetes after
repeated subcutaneous insulin injection. The recent data confirm the toxic effect of aggregates
on the cells, however, it was found that reduction of amyloid aggregates plays
important role in prevention as well as therapy of amyloidosis. We investigated capability
of phytoalexin derivatives to affect the insulin amyloid aggregation. Phytoalexins are
low molecular weight secondary metabolites produced by plants after their exposure to
biological or physical stress. By ThT and ANS fluorescence assays, the efficiency of derivatives
to inhibit formation of amyloid aggregates and depolymerize pre-formed amyloid
fibrils was studied. We identified very effective phytoalexin derivates, benzocamalexin
and cyclobrassinin, with significant inhibiting and depolymerizing activities. For these
derivatives, the determined IC50 and DC50 values are at low micromolar concentrations.
Our data suggest the potential therapeutic use of the most effective phytoalexins in the
reduction of insulin amyloid aggregation.
Acknowledgements: This work was supported within the projects Nos. 26220220005,
26220120033 and 26220120021 in frame of SF EU, Centre of Excellence of SAS Nanofluid,
VEGA 0079, 0056 and VVGS PF 13/2010/Ch.
XXII. Biochemistry Congress, Martin
211