Egg yolk, the major source of nutrition for developing chicks, is comprised largely of VLDLy, yolk-targeted particles secreted by hepatocytes of laying hens. Preliminary data show that bird kidney also secretes generic VLDL Long-term goals are to discover mechanisms by which generic VLDL and VLDLy are assembled within the lumen of the endoplasmic reticulum (ER) of apo B expressing cells. A major focus of this research is to test the hypothesis that apo B-100 (like apo B-48) is core-lipiated by two separable steps. Birds provide a unique native setting for study because: they express only apo B-100 estrogen upregulates VLDLy secretion 4-6 fold; and VLDLy are one-half the diameter of generic VLDL despite abundant lipid substrate.
Specific Aim 1 will characterize the biochemical properties of first-step and second- step particle isolated from lumenal contain of a novel ER fraction. Nascent lipoproteins from bird kidney will also be characterized for the first time. No ultrastructural studies have been published on bird VLDL or VLDLy assembly and secretion.
Specific Aim 2 is designed to compare the subcellular characteristics of bird hepatic VLDL and VLDLy secretion to bird kidney VLDL secretion. A novel nutritional hypothesis for a physiological role for kidney VLDL secretion will be investigated. Virtually nothing is known about the assembly of apo B-dividend, TG-rich second-step particles.
Specific Aim 3 is designed to discover unique second-step assembly proteins, in a novel ER fraction, that may be upregulated many fold by estrogen. Isolation and characterization of these putative second step particle assembly proteins would have a profound impact of the field of apo B biology, in both normal bird nutrition and human atheroaclerosis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL060844-03
Application #
6184815
Study Section
Nutrition Study Section (NTN)
Project Start
1998-07-15
Project End
2002-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
3
Fiscal Year
2000
Total Cost
$300,777
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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