Interaction of filipin and derivatives with erythrocyte membranes and lipid dispersions: Electron microscopic observations

Kinsky, Stephen C.; Luse, Sarah A.; Zopf, David; Deenen, L.L.M. Van; Haxby, James A.

doi:10.1016/0005-2736(67)90055-7

Cited by 109 publications

(50 citation statements)

References 12 publications

(1 reference statement)

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“…Dispersions prepared by mixture of ethanolic solutions of the steroid with an excess of water have been observed by electron microscopy of negatively stained preparations to consist of "microcrystals" of various shapes and sizes (40,41 …”

Section: Resultsmentioning

confidence: 99%

Fluorescence Studies of the Binding of the Polyene Antibiotics Filipin III, Amphotericin B, Nystatin, and Lagosin to Cholesterol

Bittman

Fischkoff

1972

Proc. Natl. Acad. Sci. U.S.A.

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The interactions of filipin III, amphotericin B, nystatin, and lagosin with sterols in aqueous suspension and in vesicles were followed by fluorescence excitation spectra and by measurement of polarized fluorescence intensities. The equilibrium constants for association of the polyene antibiotics with aqueous suspensions of cholesterol follow the order filipin IIl > amphotericin B > nystatin > lagosin, in agreement with the order reported for the extent of damage these antibiotics cause in natural and model membranes. Fluorescence polarization measurements show that hydrophobic forces are primarily responsible for the formation of the complexes. Filipin III undergoes a large enhancement in fluorescence polarization on binding to aqueous suspensions of cholesterol and epi-cholesterol, and to vesicles of lecithin-cholesterol, lecithin-fl-cholestanol, and lecithinergosterol. Small increases in polarization occur on interaction of filipin III with vesicles derived from lecithin and epi-cholesterol, thiocholesterol, and androstan-36-ol. Amphotericin B undergoes a relatively constant enhancement in fluorescence polarization on interaction with the various lecithin-sterol vesicles used and does not display the selectivity exhibited by filipin III. It is suggested that filipin IlI serves as a probe of lecithin-sterol interaction.Polyene antibiotics are potent antifungal agents produced by Streptomycetes. In addition to their ability to inhibit the sporulation and growth of yeast and other fungi (1), some of the polyene antibiotics possess antiprotozoal activity (2) and, despite their toxicity, they have clinical applicability. For example, polyene antibiotics appear to be capable of controlling serum cholesterol levels (3, 4) and prostate malfunction (5) in dogs; they also exhibit larvicidal and chemosterilant activity in some insects, apparently by blocking the uptake of dietary cholesterol (6, 7). All have a macrolide polyhydroxylic lactone ring of more than 23 atoms, with 4-7.conjugated double bonds. The discovery in 1950 of the first polyene antibiotic (8) generated considerable chemical and biological interest in this group of macrolides. The structure originally assigned to the pentaene antibiotic filipin (9-13) has been revised (14, 15) because the original work was done on a mixture of filipins (now referred to as the filipin complex) consisting of more than four components (16). The related antibiotic lagosin, which appears to be identical to, or a stereoisomer of, fungichromin, and is very similar in structure to the filipins (17), has also been subjected to extensive structural studies (11,12). Amphotericin B, a conjugated heptaene, and nystatin, whose chromophore is a conjugated tetraene distant by two methylene groups from a diene, are structurally similar. Both have a carboxyl group and an aminoglucoside group linked to the macrocyclic ring, and probably exist in the hemiketal form, at least in the crystalline state (18)(19)(20) (DMF). Experiments were done in 1 mM Tris * HCl-10 mM NaCl (pH 7.4) b...

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Section: Resultsmentioning

confidence: 99%

Fluorescence Studies of the Binding of the Polyene Antibiotics Filipin III, Amphotericin B, Nystatin, and Lagosin to Cholesterol

Bittman

Fischkoff

1972

Proc. Natl. Acad. Sci. U.S.A.

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“…Also a model proposed for the filipincholesterol complex is visualized as a complex of 15-25 nm diameter (1,3,14,32). This complex is assumed to be composed of two regular arrays of stacked filipin molecules in a lipid bilayer.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Hemolytic and Antifungal Substance, Cepalycin, from Pseudomonas cepacia

Abe

Nakazawa

1994

Microbiology and Immunology

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Hemolytic and antifungal substances, cepalycin I and cepalycin II, have been isolated from Pseudomonas cepacia JN106. A large amount of cepalycins were produced by growing the cells on 1% glycerin‐nutrient agar medium covered with a cellophane membrane. The cell‐washed supernatant was applied to an Amberlite XAD2 column, and cepalycins were eluted with 70% ethanol containing 1mM HCl. Cepalycins were separated by reverse phase HPLC in two fractions which were designated as cepalycin I and cepalycin II. The two cepalycins have indistinguishable UV absorption spectra but have different levels of hemolytic activity relative to the UV absorption. From the inhibition of hemolytic activity of cepalycin by sterols, both cepalycins were suggested to interact with cholesterol in erythrocyte membrane. Such an interaction may contribute to their hemolytic and antifungal activities.

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“…Filipin is an uncharged polyene with the highest sterol affinity. Filipin-cholesterol complexes are visualized as pits with negative staining electron microscopy [1] and as particles (100--240 i~ in diameter) in the hydrophobic core of the membrane, with freeze-fracture electron microscopy [2,3]. The filipin-sterol aggregates lead to a fragmentation of the membrane and cause release of all cytoplasmic components [4].…”

Section: Introductionmentioning

confidence: 99%

The action of pimaricin, etruscomycin and amphotericin B on liposomes with varying sterol content

Teerlink

Kruijff

Demel

1980

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Summary1. The effect of pimaricin, etruscomycin and amphotericin B on the K ÷ release from liposomes is strongly dependent on their sterol concentration.Pimaricin and etruscomycin induce K ÷ release from egg lecithin liposomes with cholesterol contents of more than 25 and 10 mol%, respectively, at polyene concentrations of 100 and 10 ~g/ml, respectively. Amphotericin B shows a maximal effect at a cholesterol content of 20 mol% at a concentration of 0.4 pg/ml.2. For liposomes containing ergosterol the sensitivity is shifted to a lower sterol content. All three l~olyenes show activity at 10 mol% ergosterol. The sensitivity for amphothericin B is increased approx. 15 times by the incorporation of ergosterol compared to cholesterol. The increase in sensitivity is much less for pimaricin and etruscomycin. The K ÷ release is maximal at an ergosterol concentration of 30 mol%.3. Pimaricin, etruscomycin and amphotericin B can induce K ÷ release from erythrocytes without the release of haemoglobin at concentrations of 20, 2 and 1/~g/ml, respectively. For these polyenes a selective permeability change is also demonstrated for liposomes since K ÷ is released but no ['4C]dextran. Filipin shows a nonselective release of solutes from erythrocytes and liposomes.4. At cholesterol concentrations higher than 20 mol% and ergosterol concentrations higher than 10 mol%, etruscomycin, pimaricin and amphotericin B show little dependence of the bflayer thickness and are able to release K ÷ from didocosenoyl phosphatidylcholine liposomes after addition of the polyene to one side of the membrane.A possible mechanism is discussed. 485

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Interaction of filipin and derivatives with erythrocyte membranes and lipid dispersions: Electron microscopic observations

Cited by 109 publications

References 12 publications

Fluorescence Studies of the Binding of the Polyene Antibiotics Filipin III, Amphotericin B, Nystatin, and Lagosin to Cholesterol

Fluorescence Studies of the Binding of the Polyene Antibiotics Filipin III, Amphotericin B, Nystatin, and Lagosin to Cholesterol

Characterization of Hemolytic and Antifungal Substance, Cepalycin, from Pseudomonas cepacia

The action of pimaricin, etruscomycin and amphotericin B on liposomes with varying sterol content

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