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Chronic ethanol intoxication induces adaptive changes at the membrane protein/lipid interface
C Ho1, B W Williams, M B Kelly
1Department of Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107.
Biochimica Et Biophysica Acta
|January 19, 1994
Summary
Chronic ethanol ingestion alters liver microsomes at the membrane protein/lipid interface. This study reveals ethanol-induced lipid changes, not protein modifications, cause this interface alteration, demonstrating membrane tolerance.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Chronic ethanol consumption is known to affect cellular membranes.
- The precise molecular alterations at the membrane protein/lipid interface due to ethanol remain incompletely understood.
Purpose of the Study:
- To investigate modifications at the membrane protein/lipid interface of liver microsomes following chronic ethanol ingestion.
- To differentiate between protein and lipid alterations contributing to observed membrane changes.
Main Methods:
- Utilized fluorescence spectroscopy with probes like 1,6-diphenyl-1,3,5-hexatriene (DPH), trimethylammonium-DPH (TMA-DPH), and a lipid-tethered probe (DPH-PC).
- Analyzed fluorescence lifetime distributions to assess environmental heterogeneity.
- Examined intact microsomes, extracted lipids, and reconstituted vesicles with a model protein (apocytochrome C).
Main Results:
- Chronic ethanol treatment increased excited-state environmental heterogeneity for all probes in intact microsomes.
- The lipid-tethered probe (DPH-PC) showed increased heterogeneity in extracted lipids, indicating ethanol-induced lipid alterations.
- Reconstituted vesicles with a model protein confirmed lipid changes, not protein modifications, were responsible for interface alterations.
- Membranes from ethanol-treated animals exhibited resistance to direct ethanol-induced heterogeneity, suggesting 'membrane tolerance' at the interface.
Conclusions:
- Chronic ethanol ingestion induces physico-chemical modifications in lipids, manifesting at the membrane protein/lipid interface.
- These findings highlight that alterations in lipid composition and dynamics, rather than direct protein modification, underlie ethanol's effects on the interface.
- The study demonstrates 'membrane tolerance' extends to the membrane protein/lipid interface, implying adaptive changes in response to chronic ethanol exposure.