| Abstract | Scavenger receptor, class B, type I (SR-BI) mediates binding and internalization of a variety of lipoprotein and nonlipoprotein ligands, including HDL. Studies in genetically engineered mice revealed that SR-BI plays an important role in HDL reverse cholesterol transport and protection against atherosclerosis. Understanding how SR-BI's function is regulated may reveal new approaches to therapeutic intervention in atherosclerosis and heart disease. We utilized a model cell system to explore pathways involved in SR-BI-mediated lipid uptake from and signaling in response to distinct lipoprotein ligands: the physiological ligand, HDL, and a model ligand, acetyl LDL (AcLDL). In Chinese hamster ovary-derived cells, murine SR-BI (mSR-BI) mediates lipid uptake via distinct pathways that are dependent on the lipoprotein ligand. Furthermore, HDL and AcLDL activate distinct signaling pathways. Finally, mSR-BI-mediated selective lipid uptake versus endocytic uptake are differentially regulated by protein kinase signaling pathways. The protein kinase C (PKC) activator PMA and the phosphatidyl inositol 3-kinase inhibitor wortmannin increase the degree of mSR-BI-mediated selective lipid uptake, whereas a PKC inhibitor has the opposite effect. These data demonstrate that SR-BI's selective lipid uptake activity can be acutely regulated by intracellular signaling cascades, some of which can originate from HDL binding to murine SR-BI itself. |
| Authors | Yi Zhang, Ayesha M Ahmed, Nicole McFarlane, Christina Capone, Douglas R Boreham, Ray Truant, Suleiman A Igdoura, Bernardo L Trigatti
(Affiliation: Departments of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.)
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| Journal | Journal of lipid research
(J Lipid Res)
Vol. 48
Issue 2
Pg. 405-16
(Feb 2007)
ISSN: 0022-2275 United States |
| PMID | 17079793
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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| Chemical References |
- Androstadienes
- Antigens, CD36
- Indoles
- Lipoproteins, HDL
- Lipoproteins, LDL
- Receptors, Lipoprotein
- acetyl-LDL
- Ro 31-8220
- wortmannin
- Protein Kinase C
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| Topics |
- Androstadienes
(pharmacology)
- Animals
- Antigens, CD36
(metabolism, pharmacology)
- Biological Transport
- CHO Cells
- Cell Line
- Cricetinae
- Cricetulus
- Female
- Indoles
(pharmacology)
- Lipid Metabolism
- Lipoproteins, HDL
(metabolism, pharmacology)
- Lipoproteins, LDL
(metabolism, pharmacology)
- Mice
- Models, Biological
- Protein Kinase C
(metabolism)
- Receptors, Lipoprotein
- Signal Transduction
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