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Ethanol-induced modifications to membrane lipid structure: effect on phospholipase A2-membrane interactions.
C D Stubbs1, B W Williams, C L Pryor
1Department of Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Archives of Biochemistry and Biophysics
|May 1, 1988
Summary
Chronic ethanol intake causes "membrane tolerance," a resistance to lipid changes. This study shows that ethanol-treated rats develop altered liver microsome lipid structures, making them resistant to phospholipase A2 action.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Chronic ethanol intoxication induces
- membrane tolerance,
- a resistance to ethanol's lipid-disordering effects.
- Existing spectroscopic methods indirectly detect this tolerance, raising questions about underlying lipid structural changes.
Purpose of the Study:
- To investigate whether chronic ethanol ingestion alters membrane lipid structure.
- To explore the mechanism of ethanol-induced membrane tolerance.
Main Methods:
- Assessing resistance to exogenous phospholipase A2 hydrolysis in liver microsomes from chronically ethanol-treated and control rats.
- Examining reconstituted lipid vesicles prepared from extracted phospholipids.
- Utilizing a specific phospholipid substrate (1-palmitoyl-2-N-(4-nitrobenzo-2-oxa-1,3-diazole)amino caproylphosphatidylcholine).
- Investigating the effect of oleic acid on phospholipase A2 resistance.
Main Results:
- Liver microsomes from ethanol-treated rats showed relative resistance to phospholipase A2.
- This resistance was maintained in reconstituted lipid vesicles.
- Increasing oleic acid levels progressively reduced the ethanol-induced resistance to hydrolysis.
Conclusions:
- Chronic ethanol treatment modifies membrane lipid structure, likely at the bilayer surface.
- Exogenous phospholipase A2 serves as a novel tool for probing ethanol-induced structural modifications.
- Membrane tolerance involves alterations in lipid structure, not just indirect detection.