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The Role of Sphingolipids in Cholesterol Efflux Mediated by ATP-Binding Cassette Transporter AI (ABCAI)

Witting, Scott R
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1089749086

Abstract Details

2004, PhD, University of Cincinnati, Medicine : Pathobiology and Molecular Medicine.
Cardiovascular disease, including stroke and atherosclerosis, remains a major cause of morbidity and mortality in the United States due to consumption of a high-fat “Western” diet. A major indication of these disease states is excess lipid deposition, particularly cholesterol, in the arterial walls. It has been well documented that high levels of circulating high-density lipoprotein (HDL) and its main protein component apolipoprotein AI (apoA-I) are associated with lowered risk of cardiovascular disease. The protective effects of HDL are thought to be mediated by a process called reverse cholesterol transport - in which HDL takes up excess cholesterol from peripheral tissues and transports it to the liver for excretion in the bile. It is now widely accepted that the interaction of apoA-I with the cell membrane protein ATP-binding cassette transporter AI (ABCAI) is critical for the formation of nascent HDL particles. Since sphingomyelin maintains a preferential interaction with cholesterol in membranes, the breakdown of sphingomyelin may regulate the availability of cellular cholesterol utilized by ABCAI. Furthermore, the catabolite of sphingomyelin, ceramide, is a potent signaling molecule and may play an important role in ABCAI regulation or function. The following study examines the potential contribution of sphingolipids in ABCAI-mediated cholesterol removal from the cell. It was discovered that treatment with C2-ceramide enhances cholesterol release to apoA-I. This effect appeared to becaused by an increase in cellular ABCAI content with enrichment at the cell surface. These findings may lead to new ways to increase cellular ABCAI and further promote cholesterol removal from regions of excess cholesterol such as the atherosclerotic lesion.
Dr. William Davidson (Advisor)
139 p.
Cholesterol; Sphingolipids; Atherosclerosis; ABC Transporter; Apolipoprotein AI; High Density Lipoprotein

Recommended Citations

Citations

  • Witting, S. R. (2004). The Role of Sphingolipids in Cholesterol Efflux Mediated by ATP-Binding Cassette Transporter AI (ABCAI) [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1089749086

    APA Style (7th edition)

  • Witting, Scott. The Role of Sphingolipids in Cholesterol Efflux Mediated by ATP-Binding Cassette Transporter AI (ABCAI). 2004. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1089749086.

    MLA Style (8th edition)

  • Witting, Scott. "The Role of Sphingolipids in Cholesterol Efflux Mediated by ATP-Binding Cassette Transporter AI (ABCAI)." Doctoral dissertation, University of Cincinnati, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1089749086

    Chicago Manual of Style (17th edition)

ucin1089749086
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© 2004, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.