Effects of 6-epi-ophiobolin A on mechanical and physiological parameters of cardiomyocytes and on the reorganization and amounts of their kv4.x ion channels

Ophiobolins are important members of the family of phytotoxic metabolites, and they possess antitumor, antibacterial, antifungal activities. At the same time, the knowledge on the effect of ophiobolins on ion channels is very limited. The voltage-dependent transient outward currents (I to) are deter...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Szűts Viktória
Ötvös Ferenc
Bencsik Ottó
Váró György
Jarabin János András
Kovács András
Rovó László
Kiss József Géza
Szénási Tibor
Véha Antal
Szekeres András
Vágvölgyi Csaba
Halasy Katalin
Szegletes Zsolt
Dokumentumtípus: Cikk
Megjelent: 2016
Sorozat:Acta biologica Szegediensis 60 No. 2
Kulcsszavak:Kardiológia, Kardiomiopátia
Online Access:http://acta.bibl.u-szeged.hu/47602
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245 1 0 |a Effects of 6-epi-ophiobolin A on mechanical and physiological parameters of cardiomyocytes and on the reorganization and amounts of their kv4.x ion channels  |h [elektronikus dokumentum] /  |c  Szűts Viktória 
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490 0 |a Acta biologica Szegediensis  |v 60 No. 2 
520 3 |a Ophiobolins are important members of the family of phytotoxic metabolites, and they possess antitumor, antibacterial, antifungal activities. At the same time, the knowledge on the effect of ophiobolins on ion channels is very limited. The voltage-dependent transient outward currents (I to) are determined by kv4.2 and kv4.3 ion channels. Increasing evidence points to a role of HMGB1 and synapse-associated protein 97 (Sap97) as underlying factors related to inflammation. The Sap97 associates with kv4.x type channels in the complex and modulating their kinetic properties. Our hypothesis was that Sap97 mainly localizes in the intercalated discs of the cardiac muscle, therefore the altered expression of ion channels is presumably involved in the inhibition of normal mechanical parameters and physiological function of transient outward current (I to). Our approach was to use purified 6-epi-ophiobolin A as effective molecular tools in the investigation of ion channels on cardiomyocytes. In this work, we have investigated the mechanical factors by atomic force microscope (AFM) technique and the surface expression of kv4 ion channels on the cardiomyocytes using confocal microscopy after immunofluorescence labeling. AFM study revealed that the elasticity of the cell surface, the Young’s modulus had been moderately changed, as well as the cell volume and the heights of the cells in the presence of low concentration of 6-epi-ophiobolin A. After this treatment the Sap97 binding to kv4.3 or kv4.2 channels and distribution of their complexes are also changed in the membrane accompanied by altered physiological behavior of cardiomyocytes as compared to control. A growing number of researches using these new reductionist models of inflammation on cardiomyocytes, demonstrate a role of Sap97 in specific ion channel stability important for cardiac functions. These results suggest that Sap97 deactivation or reduction can lead (directly or indirectly) to changes in the functional cell surface expression of kv4.x channels with mechanical parameters, with biophysical and biochemical properties of cardiac I to current. 
695 |a Kardiológia, Kardiomiopátia 
700 0 1 |a Ötvös Ferenc  |e aut 
700 0 1 |a Bencsik Ottó  |e aut 
700 0 1 |a Váró György  |e aut 
700 0 1 |a Jarabin János András  |e aut 
700 0 1 |a Kovács András  |e aut 
700 0 1 |a Rovó László  |e aut 
700 0 1 |a Kiss József Géza  |e aut 
700 0 1 |a Szénási Tibor  |e aut 
700 0 1 |a Véha Antal  |e aut 
700 0 1 |a Szekeres András  |e aut 
700 0 1 |a Vágvölgyi Csaba  |e aut 
700 0 1 |a Halasy Katalin  |e aut 
700 0 1 |a Szegletes Zsolt  |e aut 
856 4 0 |u http://acta.bibl.u-szeged.hu/47602/1/60157.pdf  |z Dokumentum-elérés