Abstract

Studies examining effects of ethanol and/or aging on membrane fluidity and composition have reported on changes in the bulk membrane. However, the membrane consists of two monolayers or leaflets that do not appear to be coupled and are structurally and compositionally asymmetric. Data on ethanol-induced changes and changes with age have been an average of the two leaflets. Using a new method to determine membrane domains, we have recently found that the outer leaflet of synaptic plasma membranes (SPM) is more fluid as compared to the inner leaflet and that ethanol in vitro had a greater effect on the outer leaflet. This asymmetric effect of ethanol may be necessary for transmembrane function in response to ethanol, e.g., enzyme activity, transport, receptoreffector complex. Such an effect may not be present in membranes of aged animals as a result of age changes in membrane asymmetry resulting from changes in lipid distribution between the two leaflets with increasing age. This hypothesis will be tested using biophysical and biochemical procedures to examine the transbilayer structural and compositional properties of SPM from 6, 18, and 30 month old C578BL/6NNIA mice. The experiments in this application will address the following issues: 1) What are the effects of ethanol in vitro (i.e., fluidity) and in vivo (i.e., fluidity, lipid distribution) on the outer and inner leaflets of SPM?; 2) Does fluidity and lipid asymmetry change with increasing age and are there age differences in effects of ethanol in vitro and in vivo on the individual membrane leaflets?; 3) What is the duration of ethanol- induced changes in SPM leaflets upon withdrawal and is this age- related?; and 4) Will modification of membrane asymmetry alter age differences in response to ethanol. The proposed work will examine for the first time the effects of ethanol on the outer and inner membrane leaflets. It is our intention that the results of the proposed studies will provide new insight into effects of ethanol on membrane domains, data on age changes in membranes and procedures that might alter changes in membranes induced by ethanol and aging.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
2R01AA007292-05A1
Application #
3111044
Study Section
Biochemistry, Physiology and Medicine Subcommittee (ALCB)
Project Start
1989-05-01
Project End
1994-02-28
Budget Start
1991-03-01
Budget End
1992-02-29
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Wood, W Gibson; Igbavboa, Urule; Muller, Walter E et al. (2011) Cholesterol asymmetry in synaptic plasma membranes. J Neurochem 116:684-9
Schroeder, F; Colles, S M; Kreishman, G P et al. (1994) Synaptic plasma membrane structure and polarity of long-sleep and short-sleep mice. Arch Biochem Biophys 309:369-76
Woodford, J K; Jefferson, J R; Wood, W G et al. (1993) Expression of liver fatty acid binding protein alters plasma membrane lipid composition and structure in transfected L-cell fibroblasts. Biochim Biophys Acta 1145:257-65
Rao, A M; Igbavboa, U; Semotuk, M et al. (1993) Kinetics and size of cholesterol lateral domains in synaptosomal membranes: modification by sphingomyelinase and effects on membrane enzyme activity. Neurochem Int 23:45-52
Sun, G Y; Navidi, M; Yoa, F G et al. (1993) Effects of chronic ethanol administration on poly-phosphoinositide metabolism in the mouse brain: variance with age. Neurochem Int 22:11-7
Incerpi, S; Jefferson, J R; Wood, W G et al. (1992) Na pump and plasma membrane structure in L-cell fibroblasts expressing rat liver fatty acid binding protein. Arch Biochem Biophys 298:35-42
Wood, W G; Gorka, C; Johnson, J A et al. (1991) Chronic ethanol consumption alters transbilayer distribution of phosphatidylcholine in erythrocytes of Sinclair (S-1) miniature swine. Alcohol 8:395-9
Schroeder, F; Jefferson, J R; Kier, A B et al. (1991) Membrane cholesterol dynamics: cholesterol domains and kinetic pools. Proc Soc Exp Biol Med 196:235-52
Schroeder, F; Nemecz, G; Wood, W G et al. (1991) Transmembrane distribution of sterol in the human erythrocyte. Biochim Biophys Acta 1066:183-92
Wood, W G; Schroeder, F; Rao, A M (1991) Significance of ethanol-induced changes in membrane lipid domains. Alcohol Alcohol Suppl 1:221-5

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