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Dissertation
Efflux and plasma transport of biosynthetic desmosterol
Doctor of Philosophy (Ph.D.), Allegheny University of the Health Sciences
Jul 1998
DOI:
https://doi.org/10.17918/00009166
Abstract
Previous work shows that the efflux of biosynthetic desmosterol from cells is three times more efficient than that of cholesterol. We wanted to determine the mechanism of this enhanced release. We labeled CHO-K1 cells with (3H) acetate precursor and measured sterols in the whole cells, plasma membranes and caveolae, and those released to high density lipoprotein (HDL3). The (3H) desmosterol-to-(3H) cholesterol ratio was similar in the plasma membrane and whole cells, but was greater in HDL3, suggesting that the more efficient efflux of desmosterol is due to more rapid desorption from the plasma membrane. The ratio in caveolae was similar to that in whole cells, arguing against selective delivery of desmosterol to caveolae as an explanation for the more rapid efflux of this sterol. Additionally, to demonstrate that the enhanced release of desmosterol was not due to enhanced intracellular cycling, we made vesicles from CHO-cell plasma membranes labeled with (3H) desmosterol or (14C) cholesterol, and desmosterol was released three times more rapidly than cholesterol. To determine if this enhanced release occurred without cellular membrane proteins, we measured the transfer of cholesterol and desmosterol between large unilamellar vesicles (LUV), and found that the transfer of desmosterol was two to three times more rapid than cholesterol. A similar differential was seen when HDL3 or low density lipoprotein (LDL) served as the acceptor for the LUV donors. These results show that the greater efflux efficiency of biosynthetic desmosterol can be attributed to more efficient desorption from the plasma membrane, and that this difference is a property of the sterols' association with the lipid bilayer. In vivo, the rapid efflux of biosynthetic sterol intermediates, followed by efficient delivery to the liver, may constitute an important mechanism for preventing the various types of pathology associated with these materials.
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Details
- Title
- Efflux and plasma transport of biosynthetic desmosterol
- Creators
- Jane Ellen Phillips
- Contributors
- William J. Johnson (Advisor) - Drexel University, Allegheny University of the Health Sciences (1996-1998)
- Awarding Institution
- Allegheny University of the Health Sciences
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Allegheny University of the Health Sciences; Philadelphia, Pennsylvania
- Number of pages
- xiv, 181 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Allegheny University of the Health Sciences (1996-1998)
- Other Identifier
- 991021888781004721