The fate of HDL particles in vivo after SR-BI-mediated selective lipid uptake
Scavenger receptor class B type I (SR-33444403) delivers cholesterol ester from HDL to cells via a selective uptake mechanism, whereby lipid is transferred from the core of the particle without concomitant degradation of the protein moiety. The precise metabolic fate of HDL particles after selective...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2002-11-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520327644 |
| _version_ | 1819072655318319104 |
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| author | Nancy R. Webb Lei Cai Kristine S. Ziemba Jin Yu Mark S. Kindy Deneys R. van der Westhuyzen Frederick C. de Beer |
| author_facet | Nancy R. Webb Lei Cai Kristine S. Ziemba Jin Yu Mark S. Kindy Deneys R. van der Westhuyzen Frederick C. de Beer |
| author_sort | Nancy R. Webb |
| collection | DOAJ |
| description | Scavenger receptor class B type I (SR-33444403) delivers cholesterol ester from HDL to cells via a selective uptake mechanism, whereby lipid is transferred from the core of the particle without concomitant degradation of the protein moiety. The precise metabolic fate of HDL particles after selective lipid uptake is not known. To characterize SR-BI-mediated HDL processing in vivo, we expressed high levels of this receptor in livers of apoA-I−/− mice by adenoviral vector gene transfer, and then injected the mice with a bolus of human HDL2 traced with 125I-dilactitol tyramine. HDL recovered from apoA-I−/− mice over-expressing SR-BI was significantly smaller than HDL recovered from control mice as measured by non-denaturing gel electrophoresis. When injected into C57BL/6 mice, these HDL “remnants” were rapidly converted to HDL2-sized lipoprotein particles, and were cleared from the plasma at a rate similar to HDL2. In assays in cultured cells, HDL remnants did not stimulate ATP-binding cassette transporter A1-dependent cholesterol efflux. When mixed with mouse plasma ex vivo, HDL remnants rapidly converted to larger HDL particles. These studies identify a previously ill-defined pathway in HDL metabolism, whereby SR-BI generates small, dense HDL particles that are rapidly remodeled in plasma.This remodeling pathway may represent a process that is important in determining the rate of apoA-I catabolism and HDL-mediated reverse cholesterol transport. |
| first_indexed | 2024-12-21T17:41:11Z |
| format | Article |
| id | doaj.art-6191ab3380c644e7b9e9b438ebb2171c |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-21T17:41:11Z |
| publishDate | 2002-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-6191ab3380c644e7b9e9b438ebb2171c2022-12-21T18:55:37ZengElsevierJournal of Lipid Research0022-22752002-11-01431118901898The fate of HDL particles in vivo after SR-BI-mediated selective lipid uptakeNancy R. Webb0Lei Cai1Kristine S. Ziemba2Jin Yu3Mark S. Kindy4Deneys R. van der Westhuyzen5Frederick C. de Beer6Departments of Internal Medicine, University of Kentucky Medical Center, Lexington, Kentucky 40536; Biochemistry, University of Kentucky Medical Center, Lexington, Kentucky 40536; Department of Veterans Affairs Medical Center, Lexington, Kentucky 40511Departments of Internal Medicine, University of Kentucky Medical Center, Lexington, Kentucky 40536; Biochemistry, University of Kentucky Medical Center, Lexington, Kentucky 40536; Department of Veterans Affairs Medical Center, Lexington, Kentucky 40511Departments of Internal Medicine, University of Kentucky Medical Center, Lexington, Kentucky 40536; Biochemistry, University of Kentucky Medical Center, Lexington, Kentucky 40536; Department of Veterans Affairs Medical Center, Lexington, Kentucky 40511Departments of Internal Medicine, University of Kentucky Medical Center, Lexington, Kentucky 40536; Biochemistry, University of Kentucky Medical Center, Lexington, Kentucky 40536; Department of Veterans Affairs Medical Center, Lexington, Kentucky 40511Departments of Internal Medicine, University of Kentucky Medical Center, Lexington, Kentucky 40536; Biochemistry, University of Kentucky Medical Center, Lexington, Kentucky 40536; Department of Veterans Affairs Medical Center, Lexington, Kentucky 40511Departments of Internal Medicine, University of Kentucky Medical Center, Lexington, Kentucky 40536; Biochemistry, University of Kentucky Medical Center, Lexington, Kentucky 40536; Department of Veterans Affairs Medical Center, Lexington, Kentucky 40511Departments of Internal Medicine, University of Kentucky Medical Center, Lexington, Kentucky 40536; Biochemistry, University of Kentucky Medical Center, Lexington, Kentucky 40536; Department of Veterans Affairs Medical Center, Lexington, Kentucky 40511Scavenger receptor class B type I (SR-33444403) delivers cholesterol ester from HDL to cells via a selective uptake mechanism, whereby lipid is transferred from the core of the particle without concomitant degradation of the protein moiety. The precise metabolic fate of HDL particles after selective lipid uptake is not known. To characterize SR-BI-mediated HDL processing in vivo, we expressed high levels of this receptor in livers of apoA-I−/− mice by adenoviral vector gene transfer, and then injected the mice with a bolus of human HDL2 traced with 125I-dilactitol tyramine. HDL recovered from apoA-I−/− mice over-expressing SR-BI was significantly smaller than HDL recovered from control mice as measured by non-denaturing gel electrophoresis. When injected into C57BL/6 mice, these HDL “remnants” were rapidly converted to HDL2-sized lipoprotein particles, and were cleared from the plasma at a rate similar to HDL2. In assays in cultured cells, HDL remnants did not stimulate ATP-binding cassette transporter A1-dependent cholesterol efflux. When mixed with mouse plasma ex vivo, HDL remnants rapidly converted to larger HDL particles. These studies identify a previously ill-defined pathway in HDL metabolism, whereby SR-BI generates small, dense HDL particles that are rapidly remodeled in plasma.This remodeling pathway may represent a process that is important in determining the rate of apoA-I catabolism and HDL-mediated reverse cholesterol transport.http://www.sciencedirect.com/science/article/pii/S0022227520327644scavenger receptoradenovirusABCA1mousereverse cholesterol transportlipoprotein |
| spellingShingle | Nancy R. Webb Lei Cai Kristine S. Ziemba Jin Yu Mark S. Kindy Deneys R. van der Westhuyzen Frederick C. de Beer The fate of HDL particles in vivo after SR-BI-mediated selective lipid uptake Journal of Lipid Research scavenger receptor adenovirus ABCA1 mouse reverse cholesterol transport lipoprotein |
| title | The fate of HDL particles in vivo after SR-BI-mediated selective lipid uptake |
| title_full | The fate of HDL particles in vivo after SR-BI-mediated selective lipid uptake |
| title_fullStr | The fate of HDL particles in vivo after SR-BI-mediated selective lipid uptake |
| title_full_unstemmed | The fate of HDL particles in vivo after SR-BI-mediated selective lipid uptake |
| title_short | The fate of HDL particles in vivo after SR-BI-mediated selective lipid uptake |
| title_sort | fate of hdl particles in vivo after sr bi mediated selective lipid uptake |
| topic | scavenger receptor adenovirus ABCA1 mouse reverse cholesterol transport lipoprotein |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520327644 |
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