Functional consequences of oxidative membrane damage

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 und...

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Bibliographic Details
Published in:The Journal of membrane biology 2005-05, Vol.205 (1), p.1-16
Main Author: Stark, G
Format: Article
Language:English
Subjects:
Animals
Calcium-Transporting ATPases - metabolism
Cell Death
Cell Membrane - metabolism
Humans
Ion Transport
Lipid Peroxidation
Membrane Lipids - metabolism
Oxidation-Reduction
Reactive Oxygen Species - metabolism
Sarcoplasmic Reticulum - metabolism
Sodium-Potassium-Exchanging ATPase - metabolism
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Summary: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.
ISSN:0022-2631
1432-1424
DOI:10.1007/s00232-005-0753-8