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001-es BibID:	BIBFORM049177
Első szerző:	Hegyi Bence (élettanász)
Cím:	Tetrodotoxin Blockade on Canine Cardiac L-Type Ca2+ Channels Depends on pH and Redox Potential / Bence Hegyi, István Komáromi, Kornél Kistamás, Ferenc Ruzsnavszky, Krisztina Váczi, Balázs Horváth, János Magyar, Tamás Bányász, Péter P. Nánási, Norbert Szentandrássy
Dátum:	2013
ISSN:	1660-3397
Megjegyzések:	Tetrodotoxin (TTX) is believed to be one of the most selective inhibitors of voltage-gated fast Na+ channels in excitable tissues. Recently, however, TTX has been shown to block L-type Ca2+ current (ICa) in canine cardiac cells. In the present study, the TTX-sensitivity of ICa was studied in isolated canine ventricular myocytes as a function of (1) channel phosphorylation, (2) extracellular pH and (3) the redox potential of the bathing medium using the whole cell voltage clamp technique. Fifty-five micromoles of TTX (IC50 value obtained under physiological conditions) caused 60% ? 2% inhibition of ICa in acidic (pH = 6.4), while only a 26% ? 2% block in alkaline (pH = 8.4) milieu. Similarly, the same concentration of TTX induced 62% ? 6% suppression of ICa in a reductant milieu (containing glutathione + ascorbic acid + dithiothreitol, 1 mM each), in contrast to the 31% ? 3% blockade obtained in the presence of a strong oxidant (100 ?M H2O2). Phosphorylation of the channel protein (induced by 3 ?M forskolin) failed to modify the inhibiting potency of TTX; an IC50 value of 50 ? 4 ?M was found in forskolin. The results are in a good accordance with the predictions of our model, indicating that TTX binds, in fact, to the selectivity filter of cardiac L-type Ca channels.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban tetrodotoxin calcium current dog heart pH dependence redox potential
Megjelenés:	Marine Drugs [electronic resource]. - 11 : 6 (2013), p. 2140-2153. -
További szerzők:	Komáromi István (1957-) (vegyész, molekuláris biológus, biokémikus) Kistamás Kornél (1986-) (biológus) Ruzsnavszky Ferenc (1984-) (élettanász) Váczi Krisztina (1987-) (élettanász) Horváth Balázs (1981-) (élettanász) Magyar János (1961-) (élettanász) Bányász Tamás (1960-) (élettanász) Nánási Péter Pál (1956-) (élettanász) Szentandrássy Norbert (1976-) (élettanász)
Pályázati támogatás:	K100151 OTKA NK104331 OTKA K101196 OTKA PD101171 OTKA TÁMOP-4.2.2.A-11/1/KONV-2012-0045 TÁMOP Élettan Kutatócsoport
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001-es BibID:	BIBFORM050047
Első szerző:	Király Anna
Cím:	Hypoxia reduces the efficiency of elisidepsin by inhibiting hydroxylation and altering the structure of lipid rafts / Anna Király, Tímea Váradi, Tímea Hajdu, Ralph Rühl, Carlos M. Galmarini, János Szöllősi, Peter Nagy
Dátum:	2013
Megjegyzések:	The mechanism of action of elisidepsin (PM02734, Irvalec(R)) is assumed to involve membrane permeabilization via attacking lipid rafts and hydroxylated lipids. Here we investigate the role of hypoxia in the mechanism of action of elisidepsin. Culturing under hypoxic conditions increased the half-maximal inhibitory concentration and decreased the drug's binding to almost all cell lines which was reversed by incubation of cells with 2-hydroxy palmitic acid. The expression of fatty acid 2-hydroxylase was strongly correlated with the efficiency of the drug and inversely correlated with the effect of hypoxia. Number and brightness analysis and fluorescence anisotropy experiments showed that hypoxia decreased the clustering of lipid rafts and altered the structure of the plasma membrane. Although the binding of elisidepsin to the membrane is non-cooperative, its membrane permeabilizing effect is characterized by a Hill coefficient of ~3.3. The latter finding is in agreement with elisidepsin-induced clusters of lipid raft-anchored GFP visualized by confocal microscopy. We propose that the concentration of elisidepsin needs to reach a critical level in the membrane above which elisidepsin induces the disruption of the cell membrane. Testing for tumor hypoxia or the density of hydroxylated lipids could be an interesting strategy to increase the efficiency of elisidepsin
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban analysis Anisotropy article Biophysics cell biology Cell Line Cell Membrane Cells Confocal Confocal microscopy EXPRESSION Fluorescence FLUORESCENCE ANISOTROPY Hungary lipid raft LIPID RAFTS Lipids Microscopy Research Research Support Support
Megjelenés:	Marine Drugs. - 11 : 12 (2013), p. 4858-4875. -
További szerzők:	Váradi Tímea (1982-) (okleveles vegyész) Hajdu Tímea (1991-) (biomérnök) Rühl, Ralph (1969-) (vegyész) Galmarini, Carlos M. Szöllősi János (1953-) (biofizikus) Nagy Péter (1971-) (biofizikus)
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