The research proposed in this application is carried out with the objective of obtaining basic information about the effects of sphingomyelin on biological membrane structure and properties and how these effects might be related to aging and atherosclerosis in blood vessels. The work outlined will utilize multilamellar liposome dispersions, single lamellar vesicles of various sizes and monolayers formed at an air/water interface. Liposomes will be used to study both compositional asymmetry between opposite bilayer faces and compositional domains within the plane of the bilayer in sphingomyelin-phosphatidylcholine-cholesterol systems and systems containing amino phospholipids. Studies of bilayer permeability, availability of membrane lipids as substrates for enzymes in the aqueous phase, lipid-protein interactions and membrane structure as functions of composition and temperature will be undertaken in systems exhibiting compositional domains. Details of the interactions between these lipids will be examined directly using monolayer techniques. The information already obtained from our previous work on model systems and simple biological membranes such as that of the red blood cell and enveloped viruses will be applied to the studies on more the complex systems of rat heart myocytes and rat heart fibroblasts in culture. The effect of sphingomyelin content on the physiological (rate of beating), biochemical (enzyme activities) and transport activities will be correlated with the changes of membrane organization and dynamics of the lipid and protein components. Our preliminary results on rat myocytes show a strong correlation between the sphingomyelin to phosphatidylcholine mole ratio and these properties of cells and their plasma membranes. Special attention will be given to an evaluation of the contribution of the three regions of a sphingomyelin molecule (polar, hydrophobic and interface) to the various effects of sphingomyelins in model systems and in biological membranes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL017576-14
Application #
3335379
Study Section
Biophysics and Biophysical Chemistry B Study Section (BBCB)
Project Start
1978-05-01
Project End
1990-06-30
Budget Start
1988-07-01
Budget End
1990-06-30
Support Year
14
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Barenholz, Yechezkel (2004) Sphingomyelin and cholesterol: from membrane biophysics and rafts to potential medical applications. Subcell Biochem 37:167-215
Bar, L K; Barenholz, Y; Thompson, T E (1997) Effect of sphingomyelin composition on the phase structure of phosphatidylcholine-sphingomyelin bilayers. Biochemistry 36:2507-16
Barenholz, Y; Cohen, T; Haas, E et al. (1996) Lateral organization of pyrene-labeled lipids in bilayers as determined from the deviation from equilibrium between pyrene monomers and excimers. J Biol Chem 271:3085-90
Glick, D; Barenholz, Y (1996) IgG immunoglobulins induce activation of the sphingomyelin cycle in HL-60 cells. FEBS Lett 394:237-40
Shmeeda, H; Petkova, D; Barenholz, Y (1995) Cholesterol distribution in rat heart myocytes. Am J Physiol 268:H759-66
Shmeeda, H; Petkova, D; Barenholz, Y (1994) Cholesterol homeostasis in cultures of rat heart myocytes: relationship to cellular hypertrophy. Am J Physiol 267:H1689-97
Bach, D; Miller, I R; Barenholz, Y (1993) Thermotropic behavior of phosphatidylcholine-glucosyl ceramide mixtures: effects of phospholipid acyl chain composition and interaction with water. Biophys Chem 47:77-86
Borenstain-Ben Yashar, V; Barenholz, Y; Hy-Am, E et al. (1993) Phosphatidylserine in the outer leaflet of red blood cells from beta-thalassemia patients may explain the chronic hypercoagulable state and thrombotic episodes. Am J Hematol 44:63-5
Kalmanzon, E; Zlotkin, E; Cohen, R et al. (1992) Liposomes as a model for the study of the mechanism of fish toxicity of sodium dodecyl sulfate in sea water. Biochim Biophys Acta 1103:148-56
Ben-Yashar, V; Barenholz, Y (1991) Characterization of the core and surface of human plasma lipoproteins. A study based on the use of five fluorophores. Chem Phys Lipids 60:1-14

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