Effects of Ionizing Radiation on Artificial (Planar) Lipid Membranes. I. Radiation Inactivation of the Ion Channel Gramicidin A

Strässle, Manuel; Stark, G.; Wilhelm, Martin

doi:10.1080/09553008714550761

Cited by 20 publications

(11 citation statements)

References 34 publications

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“…The time constants for both exponentials varied approximately in proportion to the number of Trps present, consistent with the concept that photolysis of any one of the Trps inactivates the channel. Similar results were found with ionizing X irradiation (149,150), although the mechanism was shown to involve the reaction of free radicals with the Trps. Neither UV-nor X-irradiation are effective with gramicidin M-, which contains Phe in place of each Trp.…”

Section: Radiol Ysis and Photolysissupporting

confidence: 87%

The Use of Physical Methods in Determining Gramicidin Channel Structure and Function

Busath

1993

Annu. Rev. Physiol.

124

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The various details provided by physical methods have been integrated into a coherent picture of the cation transport process. The free energy profile describes simultaneously the thermodynamic and kinetic factors that govern conductance. Localization of ion binding sites near each end of the channel by NMR and X-ray crystallographic techniques demonstrates that there is an energy barrier separating the two ends. There is no a priori reason to suspect any barrier to ion entry into the channel, and recent molecular modeling computations confirm this intuition. Therefore, the channel is best described as a two-site, one-barrier channel. However, the movement of ions across the central barrier over a distance of 1.9 nm is really a multistep process best described as Brownian motion (even the short steps from one pair of carbonyls to the next is more diffusive than activated for ions as large as Na+), the entry step is probably best considered as a compound step requiring correction for interfacial polarization and diffusion limitation, the binding sites in the channel ought not be considered to be in equilibrium with the bath, and quasi-knock off behavior (binding of a second ion at the entry facilitates release of a first ion from the exit) is probably the rule at physiological permeant ion concentrations and higher. Progress will probably focus on channel kinetics. The channel backbone probably undergoes conformational changes as the ions pass which, according to solid state NMR results, may last long enough to provide the channel with a sort of memory and which may give rise to excess single channel noise. These conformational changes are further reflected in shifts in side chain positions which, in turn, may be partly responsible for changes in the single-channel lifetime, which appears to be exquisitely sensitive to side chain-lipid interactions. Reasonable explanations for the impermeance of divalent cations, anions, and medium-sized organic cations such as guanidinium have proven elusive at first, but it now appears that divalent cations bind water too tightly, anions bind water in an orientation that produces unfavorable contacts between water oxygens and peptide carbonyl oxygens at the channel entry, and iminium ions bind strongly to the flexible peptide carbonyls at the channel entry.

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Section: Radiol Ysis and Photolysissupporting

confidence: 87%

The Use of Physical Methods in Determining Gramicidin Channel Structure and Function

Busath

1993

Annu. Rev. Physiol.

124

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“…Experiments using different radical scavengers [35] have indicated that channel inactivation by radiolysis is due to a subsequent reaction of OH and HO 2 radicals with Trp residues of gA. Ethanol is frequently used to chemically block some species of free radicals produced by irradiation [22]. In our experiments a concentration of 10% of ethanol in the buffer used to prepare the liposomes almost completely prevented the effect of irradiation, in good agreement with the results of Bonnefont-Rousselot et al [22].…”

Section: Discussionsupporting

confidence: 90%

“…Another phenomenon associated with radiation-induced lipid peroxidation was the increase of membrane capacitance [18] explained in terms of increase of the membrane dielectrical constant. This small change of the dielectrical constant can be the cause of the large increase in membrane conductance in the presence of macrocyclic ion carriers of the valinomycin type [35].…”

Section: Discussionmentioning

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 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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“…Inactivation may result from a chemical reaction with free radicals generated by water radiolysis. The membrane conductance induced by gramicidin A is reduced by many orders of magnitude by a reaction of OH and of HO; radicals with the tryptophan residues of the peptide (7)(8)(9). The hydroxyl radical OH' and the perhydroxyl radical Ho2 (as well as other oxygen radicals) are well known for their deleterious cellular effects and have been discussed in the context with a variety of diseases ( 10).…”

Section: Introductionmentioning

confidence: 99%

“…Average dose rates (including the repetition time) of up to 104 Gy/min were used. For further details of the method of pulse radiolysis (as applied at planar lipid membranes) the reader should consult references (8) and ( 12).…”

mentioning

confidence: 99%

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

Barth¹,

Stark²,

Wilhelm³

1993

Biophysical Journal

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The phenomena reported are part of a study about the effects of ionizing radiation on membrane transport. We found that the conductance of lipid membranes in the presence of the polyene-antibiotics nystatin or amphotericin B is reduced to virtually zero following irradiation. Ion channels formed by these substances seem to represent extremely sensitive structures being inactivated by radiation doses in the range of a few Centigray (1 cGy = 1 rad) at sufficiently small dose rates. Inactivation shows a so-called inverse dose-rate behavior, i.e., at constant radiation dose the effect increases with decreasing dose rate. Similar to radiation-induced lipid peroxidation the phenomenon may be understood on the basis of a radical chain mechanism initiated by free radicals of water radiolysis. The process--via peroxidation of the polyene part of the molecules--is suggested to modify the hydrophobic exterior and to destabilize the barrel-like structure of the ion channels.

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Effects of Ionizing Radiation on Artificial (Planar) Lipid Membranes. I. Radiation Inactivation of the Ion Channel Gramicidin A

Cited by 20 publications

References 34 publications

The Use of Physical Methods in Determining Gramicidin Channel Structure and Function

The Use of Physical Methods in Determining Gramicidin Channel Structure and Function

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

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

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