Inactivation by ionizing radiation of ion channels formed by polyene antibiotics amphotericin B and nystatin in lipid membranes: an inverse dose-rate behavior

Barth, Catherine; Stark, G.; Wilhelm, Martin

doi:10.1016/s0006-3495(93)81343-2

Cited by 11 publications

(7 citation statements)

References 29 publications

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“…Consequently the radical chain mechanism represented by Eqs. 2-5 shows the same dose rate dependence as was observed previously at the inactivation of polyene channels [20] and is now reported for the inactivation of the Na/K-ATPase (Fig. 3).…”

Section: Discussionsupporting

confidence: 86%

“…3). This is similar to the inactivation of ion channels formed by the polyene antibiotics amphotericin B and nystatin in planar lipid membranes [20]. An increase in the sensitivity by 2-3 orders of magnitude has been observed in that case at sufficiently small dose rates.…”

Section: Discussionsupporting

confidence: 66%

“…They are commonly believed to represent the exterior of the ion channels formed by these substances, which are in direct contact with the surrounding lipid phase. Peroxidation of this part of the ion channel has been suggested to destabilize the channel structure, finally leading to an irreversible closure of the open channels [20].…”

Section: Discussionmentioning

confidence: 99%

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Inactivation of the Na,K‐ATPase by radiation‐induced free radicals Evidence for a radical‐chain mechanism

et al. 1994

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radicalsAbstract Free radicals produced by water radiolysis were used to study the inactivation of the enzymatic activity of the Na,K-ATPase. A decrease of the activity to virtually zero with a mono-exponential dependence on the radiation dose was observed. The inactivation process is initiated by hydroxyl radicals. This was shown by the effect of appropriate radical scavengers such as t-butanol, formate and vitamin C. In all cases a si£nificant increase in the characteristic /)37 dose of inactivation was observed. Inactivation was found to show a so-called inverse dose-rate effect, i.e. the sensitivity of the enzyme to radical attack is increased if the dose rate is reduced. The data were found to agree with the relationship I/D37 ~ lid ~12, which is known to be a strong indicator of a radical chain mechanism. This means that the inactivation, after initiation by single radicals, is amplified by a subsequent chain mechanism.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 66%

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Inactivation of the Na,K‐ATPase by radiation‐induced free radicals Evidence for a radical‐chain mechanism

et al. 1994

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“…We have previously shown that inactivation of polyene channels shows an inverse dose-rate behaviour similar to that of radiation-induced lipid peroxidation (Barth et al 1993) . We intended to provide a more detailed analysis of the radicals involved and of the mechanism of inactivation .…”

Section: Introductionmentioning

confidence: 89%

“…1 or 1 mol dm -3 NaCl typically), which were prepared across a hole in a PTFE wall (Lauger 1985) . For further experimental details, as well as for a description of the apparatus used for irradiation by 80-kV X-rays of the membrane and its aqueous environment, the reader should consult Stark (1991), Barth and Stark (1991), and Barth et al (1993) . The presence of cholesterol (or of ergosterol) is required to ensure the presence of open ion channels by the polyene antibiotic amphotericin B Holz 1973, De Kruijff andDemel 1974) .…”

Section: Methodsmentioning

confidence: 99%

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

Barth

Stark

1995

International Journal of Radiation Biology

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This paper is part of a study on the effect of ionizing radiation on ion channels in biological membranes. Ion channels formed by polyene antibiotics amphotericin B or nystatin represent clusters of conjugated double bonds. As a consequence of this structural peculiarity, the conductance of lipid membranes--in the presence of polyene channels--has been found to decrease by several orders of magnitude at comparatively small doses of ionizing radiation. The phenomenon shows an inverse dose-rate behaviour similar to that of radiation-induced lipid peroxidation. We report on experiments performed in the presence of various radical scavengers, at varying cholesterol concentrations, and with different lipids. They support the view that channel inactivation is due to free radical-induced peroxidation of the polyenes leading to a destabilization of the barrel-like structure of the ion channels. Radiation-induced channel closing is shown for the first time at the level of single-ion channels.

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Functional Consequences of Oxidative Membrane Damage

2005

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The interaction of reactive oxygen species with biological membranes is known to produce a great variety of different functional modifications. Part of these modifications may be classified as direct effects. They are due to direct interaction of the reactive species with the molecular machinery under study with a subsequent chemical and functional modification of these molecules. An important part of the observed functional modifications are, however, indirect effects. They are the consequence of an oxidative modification of the environment of biological macromolecules. Lipid peroxidation-via its generation of chemically reactive products-contributes to the loss of cellular functions through the inactivation of membrane enzymes and even of cytoplasmic (i.e., water soluble) proteins. Oxidation of membrane lipids may, however, also increase the efficiency of membrane functions. This was observed for a series of transport systems. Lipid peroxidation was accompanied by activation of certain types of ion channels and ion carriers. The effect is due to an increase of the polarity of the membrane interior by accumulation of polar oxidation products. The concomitant change of the dielectric constant, which may be detected via the increase of the membrane capacitance, facilitates the opening of membrane channels and lowers the inner membrane barrier for the movement of ions across the membrane. The predominant effect, however, at least at a greater extent of lipid peroxidation, is the inhibition of membrane functions. The strong increase of the leak conductance contributes to the depolarization of the membrane potential, it destroys the barrier properties of the membrane and it may finally lead, via an increase of cytoplasmic Ca(2+) concentration, to cell death. The conclusions were derived from experiments performed with different systems: model systems in planar lipid membranes, native ion channels either reconstituted in lipid membranes or investigated in their natural environment by the patch-clamp method, and two important ion pumps, the Na/K-ATPase and the sarcoplasmic reticulum (SR) Ca-ATPase.

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Inactivation by ionizing radiation of ion channels formed by polyene antibiotics amphotericin B and nystatin in lipid membranes: an inverse dose-rate behavior

Cited by 11 publications

References 29 publications

Inactivation of the Na,K‐ATPase by radiation‐induced free radicals Evidence for a radical‐chain mechanism

Inactivation of the Na,K‐ATPase by radiation‐induced free radicals Evidence for a radical‐chain mechanism

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

Functional Consequences of Oxidative Membrane Damage

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