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Membrane disintegration caused by the steroid saponin digitonin is related to the presence of cholesterol

Sudji, I. R.; Subburaj, Y.; Frenkel, N. 1; García-Sáez, A. J.; Wink, M.
1 Institut für Toxikologie und Genetik (ITG), Karlsruher Institut für Technologie (KIT)

Abstract:

In the present investigation we studied the molecular mechanisms of the monodesmosidic saponin digitonin on natural and artificial membranes. We measured the hemolytic activity of digitonin on red blood cells (RBCs). Also different lipid membrane models (large unilamellar vesicles, LUVs, and giant unilamellar vesicles, GUVs) in the presence and absence of cholesterol were employed. The stability and permeability of the different vesicle systems were studied by using calcein release assay, GUVs membrane permeability assay using confocal microscopy (CM) and fluorescence correlation spectroscopy (FCS) and vesicle size measurement by dynamic light scattering (DLS). The results support the essential role of cholesterol in explaining how digitonin can disintegrate biological and artificial membranes. Digitonin induces membrane permeability or causes membrane rupturing only in the presence of cholesterol in an all-or-none mechanism. This effect depends on the concentrations of both digitonin and cholesterol. At low concentrations, digitonin induces membrane permeability while keeping the membrane intact. When digitonin is combined with other drugs, a synergistic potentiation can be observed because it facilitates their uptake.


Volltext §
DOI: 10.5445/IR/1000056931
Originalveröffentlichung
DOI: 10.3390/molecules201119682
Scopus
Zitationen: 63
Web of Science
Zitationen: 57
Dimensions
Zitationen: 68
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2015
Sprache Englisch
Identifikator ISSN: 1420-3049
urn:nbn:de:swb:90-569317
KITopen-ID: 1000056931
HGF-Programm 47.01.01 (POF III, LK 01) Biol.Netzwerke u.Synth.Regulat. ITG+ITC
Erschienen in Molecules
Verlag MDPI
Band 20
Heft 11
Seiten 20146-20160
Schlagwörter Digitonin, cholesterol, calcein release, giant unilamellar vesicles, dynamic light scattering, membrane permeability
Nachgewiesen in Dimensions
Scopus
Web of Science
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