Regulation of SR-BI-mediated selective lipid uptake in Chinese hamster ovary-derived cells by protein kinase signaling pathways.

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
• Journal: Journal of lipid research (J Lipid Res) Vol. 48 Issue 2 Pg. 405-16 (Feb 2007) ISSN: 0022-2275 [Print] United States
• PMID: 17079793 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androstadienes
• CD36 Antigens
• Indoles
• Lipoproteins, HDL
• Lipoproteins, LDL
• Receptors, Lipoprotein
• acetyl-LDL
• Protein Kinase C
• Ro 31-8220
• Wortmannin

Topics

• Androstadienes (pharmacology)
• Animals
• Biological Transport
• CD36 Antigens (metabolism, pharmacology)
• 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
• Wortmannin