Abstract

The production of very low density lipoprotein and high density lipoprotein particles by the liver is a tightly regulated process, which begins with synthesis and assembly of core protein components in the rough endoplasmic reticulum. Factors influencing the production and metabolism of these particles are of immediate medical relevance, as their malfunction or hyperactivity can lead to an assortment of disease states. Hepatic lipase is a secreted liver enzyme, with many previously described roles in the metabolism and clearance of both high and low density lipoproteins. Increased production and assembly of this enzyme is an indicator of metabolic dysfunction, while its absence or insufficiency leads to pre-mature atherosclerosis and death. The present study shows that this enzyme’s role in lipoprotein metabolism is not confined to the degradation and clearance of these particles after they have been secreted. Experiments using co-immunoprecipitation targeted at hepatic lipase demonstrate that this protein interacts with ApoA1 and ApoB100, the core protein components of HDL and VLDL respectively, at the ER level in hepatocytes, as part of an enormous multi-subunit protein complex. This interaction with ApoA1 leads to decreased competence of hepatocytes to secrete HDL, which confers a pro-atherogenic phenotype. Analysis of ER to Golgi VLDL transport vesicles, produced with a cell-free in vitro budding assay, has revealed that hepatic lipase is co-secreted between these compartments with immature VLDL particles. Further analysis of cytosol isolated from hepatocytes demonstrates an interaction between hepatic lipase and the LDL-receptor related protein in a post-Golgi vesicle; the significance of which will be investigated in future studies.

Notes

This item is only available to users on the UCF campus. If this is your Honors thesis, and want to learn how to access it or for more information about readership statistics, contact us at STARS@ucf.edu

Thesis Completion

2015

Semester

Spring

Advisor

Siddiqi, Shadab

Degree

Bachelor of Science (B.S.)

College

College of Medicine

Department

Biomedical Sciences

Degree Program

Biotechnology

Subjects

Dissertations, Academic -- Medicine; Medicine -- Dissertations, Academic

Format

PDF

Identifier

CFH0004736

Language

English

Access Status

Campus-only Access

Length of Campus-only Access

5 years

Document Type

Honors in the Major Thesis

Share

COinS