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Dissertation
The role of the ATP-binding cassette transporter A1 (ABCA1) in cholesterol metabolism
Doctor of Philosophy (Ph.D.), Drexel University
Dec 2002
DOI:
https://doi.org/10.17918/00000487
Abstract
The release of cellular cholesterol and phospholipid to apolipoproteins is thought to be the initial step in high density lipoprotein (HDL) formation. HDL is the lipid carrier of reverse cholesterol transport (RCT), the process by which cholesterol is mobilized from the periphery. Patients with mutations of the ATP-Binding Cassette Transporter A1 (ABCA1) manifest low or absent HDL levels. Results from Aim 1 of this thesis confirm that ABCA1 expression stimulates cellular cholesterol release to apolipoproteins. We established that mouse macrophages, particularly the J774 cell line, are highly responsive to cAMP induction of ABCA1 activity. We used the results of Aim 1 in order to model the apolipoprotein/ABCA1/membrane interaction and studied the nature of particles released into cell conditioned medium. Cholesterol-rich, spherical particles were released from cholesterol-enriched J774 upon incubation with apo AI and data from Aim 2 suggest that ABCA1-mediated efflux is a cytoprotective mechanism for macrophages to eliminate excess cholesterol. Other cell types may be responsible for the bulk of nascent HDL formation. The results of Aim 3 show that type II lung alveolar pneumocytes express functional ABCA1. ABCA1 may modulate surfactant secretion or have a role in HDL formation in this tissue since type I cells, in direct contact with the lung vasculature, also express ABCAI. Given the presence of circulating apolipoproteins and other factors, we hypothesize that the lung may be an unrecognized site of nascent HDL synthesis.
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Details
- Title
- The role of the ATP-binding cassette transporter A1 (ABCA1) in cholesterol metabolism
- Creators
- Anna E. Bortnick
- Contributors
- George H. Rothblat (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiii, 163 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Medicine; Pharmacology and Physiology; Drexel University
- Other Identifier
- 991014970317104721