A permeability transition in liposomes induced by the formation of Ca2+/palmitic acid complexes.
Formation of palmitic acid/Ca(2+) (PA/Ca(2+)) complexes was suggested to play a key role in the non-classical permeability transition in mitochondria (NCPT), which seems to be involved in the PA-induced apoptosis of cardiomyocytes. Our previous studies of complexation of free fatty acids (FFA) with Ca(2+) showed that long-chain (C:16-C:22) saturated FFA had an affinity to Ca(2+), which was much higher than that of other FFA and lipids. The formation of FFA/Ca(2+) complexes in the black-lipid membrane (BLM) was demonstrated to induce a nonspecific ion permeability of the membrane. In the present work, we have found that binding of Ca(2+) to PA incorporated into the membrane of sulforhodamine B (SRB)-loaded liposomes results in an instant release of a part of SRB, with the quantity of SRB released depending on the concentration of PA and Ca(2+). The pH-optimum of this phenomenon, similar to that of PA/Ca(2+) complexation, is in the alkaline range. The same picture of SRB release has been revealed for stearic, but not for linoleic acid. Along with Ca(2+), some other bivalent cations (Ba(2+), Sr(2+), Mn(2+), Ni(2+), Co(2+)) also induce SRB release upon binding to PA-containing liposomes, while Mg(2+) turns out to be relatively ineffective. As revealed by fluorescence correlation spectroscopy, the apparent size of liposomes does not alter after the addition of PA, Ca(2+) or their combination. So it has been supposed that the cause of SRB release from liposomes is the formation of lipid pores. The effect of FFA/Ca(2+)-induced permeabilization of liposomal membranes has several analogies with NCPT, suggesting that both these phenomena are of similar nature.
Agafonov
Alexey
A
Laboratory Mitochondrial Transport, Institute of Theoretical and Experimental Biophysics RAS, Pushchino, Moscow Region 1422290, Russia.
Gritsenko
Elena
E
Belosludtsev
Konstantin
K
Kovalev
Alexandr
A
Gateau-Roesch
Odile
O
Saris
Nils-Erik L
NE
Mironova
Galina D
GD
D002118:Calcium / Q000737:chemistry* / Q000494:pharmacology; D002413:Cations, Divalent; D005456:Fluorescent Dyes; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D009994:Osmolar Concentration; D019308:Palmitic Acid / Q000737:chemistry*; D010539:Permeability / Q000187:drug effects; D012235:Rhodamines
D002413:Cations, Divalent; D005456:Fluorescent Dyes; D008081:Liposomes; D012235:Rhodamines; C022027:lissamine rhodamine B; D019308:Palmitic Acid; D002118:Calcium