Abstract

The overall goal of the program is to elucidate the mechanisms by which the liver maintains cholesterol homeostasis. The focus of this application is to elucidate the nature and physiology of the chylomicron remnant receptor. To this end we propose to purify the receptor, characterize it and prepare an antibody to it. This antibody will be used to elucidate the relationship if any of the low density lipoprotein receptor and the chylomicron remnant receptor. Studies to examine post binding events in remnant metabolism and to quantify the roles of individual cell types in remnant metabolism are also proposed. The influence of the physical state of the environment on apo E binding will be studied. Further work to prove our hypothesis that hepatomas have a defect in remnant metabolism is planned. Lastly, we propose to explore the nature of the lipoprotein binding sites on human liver. These studies, by describing how cholesterol entry in liver is regulated, may help us to understand the pathogenesis of both atherosclerosis and cholelithiasis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
7R01DK038318-01
Application #
3237628
Study Section
(SSS)
Project Start
1986-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Palo Alto Medical Foundation Research Institute
Department
Type
DUNS #
622276137
City
Palo Alto
State
CA
Country
United States
Zip Code
94301

  Publications

Grosskopf, Itamar; Baroukh, Nadine; Lee, Sung-Joon et al. (2005) Apolipoprotein A-V deficiency results in marked hypertriglyceridemia attributable to decreased lipolysis of triglyceride-rich lipoproteins and removal of their remnants. Arterioscler Thromb Vasc Biol 25:2573-9
Yu, Kenneth C-W; David, Christopher; Kadambi, Sujata et al. (2004) Endothelial lipase is synthesized by hepatic and aorta endothelial cells and its expression is altered in apoE-deficient mice. J Lipid Res 45:1614-23
Ishida, Tatsuro; Choi, Sungshin Y; Kundu, Ramendra K et al. (2004) Endothelial lipase modulates susceptibility to atherosclerosis in apolipoprotein-E-deficient mice. J Biol Chem 279:45085-92
Ishida, Tatsuro; Choi, Sungshin; Kundu, Ramendra K et al. (2003) Endothelial lipase is a major determinant of HDL level. J Clin Invest 111:347-55
Chen, Jean Y; Levy-Wilson, Beatriz; Goodart, Sheryl et al. (2002) Mice expressing the human CYP7A1 gene in the mouse CYP7A1 knock-out background lack induction of CYP7A1 expression by cholesterol feeding and have increased hypercholesterolemia when fed a high fat diet. J Biol Chem 277:42588-95
Yu, K C; Chen, W; Cooper, A D (2001) LDL receptor-related protein mediates cell-surface clustering and hepatic sequestration of chylomicron remnants in LDLR-deficient mice. J Clin Invest 107:1387-94
Yu, K C; Jiang, Y; Chen, W et al. (2000) Rapid initial removal of chylomicron remnants by the mouse liver does not require hepatically localized apolipoprotein E. J Lipid Res 41:1715-27
Yu, K C; Jiang, Y; Chen, W et al. (1999) Evaluation of the components of the chylomicron remnant removal mechanism by use of the isolated perfused mouse liver. J Lipid Res 40:1899-910
Cooper, A D (1999) Role of the enterohepatic circulation of bile salts in lipoprotein metabolism. Gastroenterol Clin North Am 28:211-29, viii
Choi, S Y; Goldberg, I J; Curtiss, L K et al. (1998) Interaction between ApoB and hepatic lipase mediates the uptake of ApoB-containing lipoproteins. J Biol Chem 273:20456-62

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