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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)
Internet cím:	DOI Szerző által megadott URL Intézményi repozitóriumban (DEA) tárolt változat
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