Radiation-induced and Free Radical-mediated Inactivation of Ion Channels Formed by the Polyene Antibiotic Amphotericin B in Lipid Membranes: Effect of Radical Scavengers and Single-channel Analysis

Zeidler, U.; Barth, Catherine; Stark, G.

doi:10.1080/09553009514550161

Cited by 9 publications

(4 citation statements)

References 20 publications

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“…In this way, we proved the fact that lipidic environment is one of the main causes of the gA inactivation. In the literature, a similar inverse dose-rate effect has been demonstrated by conductance modification in other ion channels, such as amphotericin B [13]. In addition, the Trp fluorescence in hydrophilic proteins (BSA) in the presence of lipid vesicles also showed an inverse dose-rate effect [28,29].…”

Section: Discussionmentioning

confidence: 70%

“…Generation of the reactive species gives rise to a decay of the membrane potential, to an inactivation of K + -channels, and to an increase of the leak conductance of the membrane [12]. Pore-forming proteins, such as gA, amphotericin B etc., inserted in artificial lipid bilayers show a decrease of their conductance upon X-ray irradiation in the 0-500 Gy dose range [12,13]. Lipids from model and natural membrane are drastically affected by radiation (e.g.…”

Section: Introductionmentioning

confidence: 99%

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A fluorescence approach of the gamma radiation effects on gramicidin A inserted in liposomes

Nae

Gazdaru

Acasandrei

et al. 2008

Journal of Peptide Science

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The fluorescence of tryptophan residues of gramicidin A (gA), bound to phosphatidylcholine liposomes contains valuable information about local changes in the environment of the molecule induced by gamma radiation. With this work, we aim to demonstrate that the gamma radiation effect on the peptide involves the action of free radicals, derived from water radiolysis and the process of lipid peroxidation. Basically, the methodology consists of the analysis of UV and fluorescence emission spectra of the peptide liposome complexes under control conditions and upon gamma irradiation. Free radical production was impaired by the removal of molecular oxygen or the presence of ethanol in the liposome suspension. The intensity of the tryptophan fluorescence was recorded as a function of the gamma radiation dose in the range of 0-250 Gy and the data were fitted with a single decay exponential function containing an additional constant term (named residual fluorescence). The correlation between the decrease in tryptophan fluorescence emission (D(c) = 80 +/- 10 Gy) and increase in gamma radiation dose indicates the partial damage of the tryptophan side chains of gA. O(2) removal or ethanol addition partially reduced the decay of the tryptophan fluorescence emission involving an indirect action of gamma radiation via a water radiolysis mechanism. The residual fluorescence emission (A(0)) increases in O(2)-free buffer (98 +/- 13) and in 10% ethanol-containing buffer (74 +/- 34) compared to control conditions (23 +/- 5). Varying the dose rate between 1-10 Gy/min at a constant dose of 50 Gy, an inverse dose-rate effect was observed. Thus, our study provides evidence for the lipid peroxidation effect on the tryptophan fluorescence. In conclusion, this article sustains the hypothesis of the connection between the lipid peroxidation and structural changes of membrane proteins induced by gamma radiation.

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Section: Discussionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

A fluorescence approach of the gamma radiation effects on gramicidin A inserted in liposomes

Nae

Gazdaru

Acasandrei

et al. 2008

Journal of Peptide Science

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“…The cell sensitivity to polyene antibiotics is determined by the lipid composition of the plasma membrane, either in the nature of the membrane sterols or the amount present [3]. For instance, the sensitivity increases with ergosterol content in Saccharomyces cere6isiae [4], whereas inactivation of the ion channels in the plasma membrane induced by the polyene antibiotics is due to free radical induced-peroxidation of the polyenes [5]. The interaction of polyene antibiotics with biomembranes results in loss of intracellular protons and small molecules [6].…”

mentioning

confidence: 99%

Specific recombinogenic activity of a new polyene antibiotic

Vachkova

Kappas

Tyagunenko

et al. 1998

CMLS, Cell. Mol. Life Sci.

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A new antibiotic from Streptomyces sp., tetrapol A159, active against various fungi, a promising compound for the control of plant diseases, was studied for its genotoxic effects. It was produced at the Institute of Microbiological Preparations for Agriculture, Sofia, Bulgaria. The chemical was tested in three different test systems: a bacterial system, the Ames test for point mutations, the micronucleus test in bone marrow cells of rats for chromosomal aberrations and the fungal system of Aspergillus nidulans for mitotic recombination and aneuploidy. No increase in histidine revertants was observed in any of the TA100, TA98, TA1535 and TA1537 strains of Salmonella at concentrations ranging from 1 to 4000 mg/plate. The results were also negative in the micronucleus test of bone marrow cells at concentrations from 124 to 600 mg/kg b.w., whereas a statistically significant threefold increase of mitotic crossovers was found in Aspergillus, at concentrations from 0.5 to 2.5 mg/ml.

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“…To this end, their effect on certain well-known model systems is considered, the normal function of which has been analyzed in great detail in the past. We have shown in previous publications that ion channels formed by the antibiotics gramicidin A (Strassle et al, 1987(Strassle et al, , 1989Strassle & Stark, 1992) or amphotericin B (Barth et al, 1993;Zeidler et al, 1995) respond very sensitively to the presence of free radicals generated by absorption of ionizing radiation in water (water radiolysis), or to visible light in the presence of photosensitizers (photodynamic inactivation). The present investigation is intended to provide a more detailed analysis of the functional consequences of radical action on the level of single gramicidin channels, and to correlate the functional aspects with stmctural changes.…”

mentioning

confidence: 99%

Photodynamic and Radiolytic Inactivation of Ion Channels Formed by Gramicidin A: Oxidation and Fragmentation

Kunz

Zeidler²,

Haegele³

et al. 1995

Biochemistry

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Ion channels formed by the peptide gramicidin A in planar lipid membranes have been reported to react very sensitively upon irradiation of the membrane by ionizing radiation (radiolysis), by UV light (photolysis), or by visible light in the presence of appropriate photosensitizers (photodynamic inactivation). In all three cases the effect is due to the presence of the four tryptophan residues of the pentadecapeptide. Modifications of these amino acids--due to an interaction with free radicals formed upon water radiolysis or due to light absorption--have been found to reduce the membrane conductance by many orders of magnitude. The present study was intended to correlate functional changes, observed at the level of single ion channels, with changes of the molecular structure identified by mass spectrometry. About 98% of the inactivated channels showed a single-channel conductance of virtually zero, while about 2% of the channels present before irradiation are converted to a state of reduced conductance (and reduced lifetime). On the structural level, irradiation in the presence of the photosensitizer Rose Bengal was found to produce oxidation and fragmentation of the peptide at the positions of the tryptophan residues. Our results provide evidence that the main effect of radiolysis, or of photodynamic treatment, is the cleavage of the peptide backbone leading to immediate closure of an open ion channel.

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Radiation-induced and Free Radical-mediated Inactivation of Ion Channels Formed by the Polyene Antibiotic Amphotericin B in Lipid Membranes: Effect of Radical Scavengers and Single-channel Analysis

Cited by 9 publications

References 20 publications

A fluorescence approach of the gamma radiation effects on gramicidin A inserted in liposomes

A fluorescence approach of the gamma radiation effects on gramicidin A inserted in liposomes

Specific recombinogenic activity of a new polyene antibiotic

Photodynamic and Radiolytic Inactivation of Ion Channels Formed by Gramicidin A: Oxidation and Fragmentation

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