Abstract

The aim is to study the structure-function relationships of the apolipoproteins. Lipoproteins play important roles in the transport of lipids through plasma and also in atherogenesis. In addition to performing lipid transport (i.e. detergent-like) functions, apolipoproteins also are responsible for modulating most of the interactions of lipoproteins with enzymes and cell receptors. Monoclonal antibodies will be produced against apolipoproteins AI, AII, B-100, B-48 and E. The numbers of distinct epitopes on each apoprotein will be enumerated using competition and cotitration assays. By means of apoprotein fragmentation, chemical modification and partial apoprotein synthesis, epitopes will be assigned to regions of apoproteins. Expression of epitopes on native hololipoproteins of normal and dyslipoproteinemic subjects and on recombinant lipoproteins will be assessed in binding assays using antibodies and Fab fragments. Epitope expression will be connected with function, e.g., epitopes of apoE will be linked to the apoB,E and apoE receptor binding domains of apoE; apoAI epitopes will be linked to the LCAT activator function of apoAI. It is hoped that these studies will contribute to knowledge of lipoprotein structure and function.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL015308-14
Application #
3334920
Study Section
Metabolism Study Section (MET)
Project Start
1976-05-01
Project End
1989-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
14
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

Parhofer, K G; Barrett, P H; Bier, D M et al. (1992) Lipoproteins containing the truncated apolipoprotein, Apo B-89, are cleared from human plasma more rapidly than Apo B-100-containing lipoproteins in vivo. J Clin Invest 89:1931-7
Parhofer, K G; Hugh, P; Barrett, R et al. (1991) Determination of kinetic parameters of apolipoprotein B metabolism using amino acids labeled with stable isotopes. J Lipid Res 32:1311-23
Kinoshita, M; Krul, E S; Schonfeld, G (1990) Modification of the core lipids of low density lipoproteins produces selective alterations in the expression of apoB-100 epitopes. J Lipid Res 31:701-8
Jiao, S; Cole, T G; Kitchens, R T et al. (1990) Genetic heterogeneity of plasma lipoproteins in the mouse: control of low density lipoprotein particle sizes by genetic factors. J Lipid Res 31:467-77
Parhofer, K G; Daugherty, A; Kinoshita, M et al. (1990) Enhanced clearance from plasma of low density lipoproteins containing a truncated apolipoprotein, apoB-89. J Lipid Res 31:2001-7
Keidar, S; Goldberg, A C; Cook, K et al. (1990) A high carbohydrate-fat free diet alters the proportion of heparin-bound VLDL in plasma and the expression of VLDL-apoB-100 epitopes. Metabolism 39:281-8
Moberly, J B; Cole, T G; Alpers, D H et al. (1990) Oleic acid stimulation of apolipoprotein B secretion from HepG2 and Caco-2 cells occurs post-transcriptionally. Biochim Biophys Acta 1042:70-80
Jiao, S; Moberly, J B; Schonfeld, G (1990) Editing of apolipoprotein B messenger RNA in differentiated Caco-2 cells. J Lipid Res 31:695-700
Keidar, S; Ostlund Jr, R E; Schonfeld, G (1990) Apolipoprotein E-rich HDL in patients with homozygous familial hypercholesterolemia. Atherosclerosis 84:155-63
Jiao, S; Moberly, J B; Cole, T G et al. (1989) Decreased activity of acyl-CoA:cholesterol acyltransferase by insulin in human intestinal cell line Caco-2. Diabetes 38:604-9

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