Regulation of SR-BI-mediated selective lipid uptake in Chinese hamster ovary-derived cells by protein kinase signaling pathwayss⃞
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 ather...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2007-02-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520436764 |
| _version_ | 1818676104195473408 |
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| author | Yi Zhang Ayesha M. Ahmed Nicole McFarlane Christina Capone Douglas R. Boreham Ray Truant Suleiman A. Igdoura Bernardo L. Trigatti |
| author_facet | Yi Zhang Ayesha M. Ahmed Nicole McFarlane Christina Capone Douglas R. Boreham Ray Truant Suleiman A. Igdoura Bernardo L. Trigatti |
| author_sort | Yi Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T08:38:10Z |
| format | Article |
| id | doaj.art-c62a1a4fd66d42548e7d74e0a755757c |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T08:38:10Z |
| publishDate | 2007-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-c62a1a4fd66d42548e7d74e0a755757c2022-12-21T21:56:26ZengElsevierJournal of Lipid Research0022-22752007-02-01482405416Regulation of SR-BI-mediated selective lipid uptake in Chinese hamster ovary-derived cells by protein kinase signaling pathwayss⃞Yi Zhang0Ayesha M. Ahmed1Nicole McFarlane2Christina Capone3Douglas R. Boreham4Ray Truant5Suleiman A. Igdoura6Bernardo L. Trigatti7Departments of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, CanadaDepartments of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, CanadaDepartments of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, CanadaDepartments of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, CanadaDepartments of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, CanadaDepartments of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, CanadaDepartments of Biology and Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, CanadaDepartments of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, CanadaScavenger 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.http://www.sciencedirect.com/science/article/pii/S0022227520436764acetyl LDLendocytosisHDLlipoproteinphosphatidyl inositol 3-kinaseprotein kinase C |
| spellingShingle | Yi Zhang Ayesha M. Ahmed Nicole McFarlane Christina Capone Douglas R. Boreham Ray Truant Suleiman A. Igdoura Bernardo L. Trigatti Regulation of SR-BI-mediated selective lipid uptake in Chinese hamster ovary-derived cells by protein kinase signaling pathwayss⃞ Journal of Lipid Research acetyl LDL endocytosis HDL lipoprotein phosphatidyl inositol 3-kinase protein kinase C |
| title | Regulation of SR-BI-mediated selective lipid uptake in Chinese hamster ovary-derived cells by protein kinase signaling pathwayss⃞ |
| title_full | Regulation of SR-BI-mediated selective lipid uptake in Chinese hamster ovary-derived cells by protein kinase signaling pathwayss⃞ |
| title_fullStr | Regulation of SR-BI-mediated selective lipid uptake in Chinese hamster ovary-derived cells by protein kinase signaling pathwayss⃞ |
| title_full_unstemmed | Regulation of SR-BI-mediated selective lipid uptake in Chinese hamster ovary-derived cells by protein kinase signaling pathwayss⃞ |
| title_short | Regulation of SR-BI-mediated selective lipid uptake in Chinese hamster ovary-derived cells by protein kinase signaling pathwayss⃞ |
| title_sort | regulation of sr bi mediated selective lipid uptake in chinese hamster ovary derived cells by protein kinase signaling pathwayss⃞ |
| topic | acetyl LDL endocytosis HDL lipoprotein phosphatidyl inositol 3-kinase protein kinase C |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520436764 |
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