title: 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.affiliation: Departments of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ayesha M
authors.initials: AM
authors.lastname: Ahmed
authors.forename: Nicole
authors.initials: N
authors.lastname: McFarlane
authors.forename: Christina
authors.initials: C
authors.lastname: Capone
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Boreham
authors.forename: Ray
authors.initials: R
authors.lastname: Truant
authors.forename: Suleiman A
authors.initials: SA
authors.lastname: Igdoura
authors.forename: Bernardo L
authors.initials: BL
authors.lastname: Trigatti
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D018955:CD36 Antigens / Q000378:metabolism* / Q000494:pharmacology; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D007211:Indoles / Q000494:pharmacology; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D011493:Protein Kinase C / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D015398:Signal Transduction; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D018955:CD36 Antigens; D007211:Indoles; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D018110:Receptors, Lipoprotein; C032629:acetyl-LDL; D011493:Protein Kinase C; C064758:Ro 31-8220; D000077191:Wortmannin