Different cellular traffic of LDL-cholesterol and acetylated LDL-cholesterol leads to distinct reverse cholesterol transport pathwayss⃞
Endocytosis of LDL and modified LDL represents regulated and unregulated cholesterol delivery to macrophages. To elucidate the mechanisms of cellular cholesterol transport and egress under both conditions, various primary macrophages were labeled and loaded with cholesterol or cholesteryl ester from...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2007-03-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520432389 |
| _version_ | 1818675695350448128 |
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| author | Ming-Dong Wang Robert S. Kiss Vivian Franklin Heidi M. McBride Stewart C. Whitman Yves L. Marcel |
| author_facet | Ming-Dong Wang Robert S. Kiss Vivian Franklin Heidi M. McBride Stewart C. Whitman Yves L. Marcel |
| author_sort | Ming-Dong Wang |
| collection | DOAJ |
| description | Endocytosis of LDL and modified LDL represents regulated and unregulated cholesterol delivery to macrophages. To elucidate the mechanisms of cellular cholesterol transport and egress under both conditions, various primary macrophages were labeled and loaded with cholesterol or cholesteryl ester from LDL or acetylated low density lipoprotein (AcLDL), and the cellular cholesterol traffic pathways were examined. Confocal microscopy using fluorescently labeled 3,3′-dioctyldecyloxacarbocyanine perchlorate-labeled LDL and 1,1′-dioctyldecyl-3,3,3′,3′-tetramethylindodicarbocyanine perchlorate-labeled AcLDL demonstrated their discrete traffic pathways and accumulation in distinct endosomes. ABCA1-mediated cholesterol efflux to apolipoprotein A-I (apoA-I) was much greater for AcLDL-loaded macrophages compared with LDL. Treatment with the liver X receptor ligand 22-OH increased efflux to apoA-I in AcLDL-loaded but not LDL-loaded cells. In contrast, at a level equivalent to AcLDL, LDL-derived cholesterol was preferentially effluxed to HDL, in keeping with increased ABCG1. In vivo studies of reverse cholesterol transport (RCT) from cholesterol-labeled macrophages injected intraperitoneally demonstrated that LDL-derived cholesterol was more efficiently transported to the liver and secreted into bile than AcLDL-derived cholesterol. This indicates a greater efficiency of HDL than lipid-poor apoA-I in interstitial fluid in controlling in vivo RCT. These assays, taken together, emphasize the importance of mediators of diffusional cholesterol efflux in RCT. |
| first_indexed | 2024-12-17T08:31:40Z |
| format | Article |
| id | doaj.art-eed66b06313444f08884b77dd64150f2 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T08:31:40Z |
| publishDate | 2007-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-eed66b06313444f08884b77dd64150f22022-12-21T21:56:36ZengElsevierJournal of Lipid Research0022-22752007-03-01483633645Different cellular traffic of LDL-cholesterol and acetylated LDL-cholesterol leads to distinct reverse cholesterol transport pathwayss⃞Ming-Dong Wang0Robert S. Kiss1Vivian Franklin2Heidi M. McBride3Stewart C. Whitman4Yves L. Marcel5Lipoprotein and Atherosclerosis Research Group, University of Ottawa Heart Institute, and Departments of Biochemistry, Microbiology, Immunology, and Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, CanadaLipoprotein and Atherosclerosis Research Group, University of Ottawa Heart Institute, and Departments of Biochemistry, Microbiology, Immunology, and Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, CanadaLipoprotein and Atherosclerosis Research Group, University of Ottawa Heart Institute, and Departments of Biochemistry, Microbiology, Immunology, and Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, CanadaLipoprotein and Atherosclerosis Research Group, University of Ottawa Heart Institute, and Departments of Biochemistry, Microbiology, Immunology, and Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, CanadaLipoprotein and Atherosclerosis Research Group, University of Ottawa Heart Institute, and Departments of Biochemistry, Microbiology, Immunology, and Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, CanadaLipoprotein and Atherosclerosis Research Group, University of Ottawa Heart Institute, and Departments of Biochemistry, Microbiology, Immunology, and Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, CanadaEndocytosis of LDL and modified LDL represents regulated and unregulated cholesterol delivery to macrophages. To elucidate the mechanisms of cellular cholesterol transport and egress under both conditions, various primary macrophages were labeled and loaded with cholesterol or cholesteryl ester from LDL or acetylated low density lipoprotein (AcLDL), and the cellular cholesterol traffic pathways were examined. Confocal microscopy using fluorescently labeled 3,3′-dioctyldecyloxacarbocyanine perchlorate-labeled LDL and 1,1′-dioctyldecyl-3,3,3′,3′-tetramethylindodicarbocyanine perchlorate-labeled AcLDL demonstrated their discrete traffic pathways and accumulation in distinct endosomes. ABCA1-mediated cholesterol efflux to apolipoprotein A-I (apoA-I) was much greater for AcLDL-loaded macrophages compared with LDL. Treatment with the liver X receptor ligand 22-OH increased efflux to apoA-I in AcLDL-loaded but not LDL-loaded cells. In contrast, at a level equivalent to AcLDL, LDL-derived cholesterol was preferentially effluxed to HDL, in keeping with increased ABCG1. In vivo studies of reverse cholesterol transport (RCT) from cholesterol-labeled macrophages injected intraperitoneally demonstrated that LDL-derived cholesterol was more efficiently transported to the liver and secreted into bile than AcLDL-derived cholesterol. This indicates a greater efficiency of HDL than lipid-poor apoA-I in interstitial fluid in controlling in vivo RCT. These assays, taken together, emphasize the importance of mediators of diffusional cholesterol efflux in RCT.http://www.sciencedirect.com/science/article/pii/S0022227520432389cholesterol effluxATP binding cassette transporter A1ATP binding cassette transporter G1scavenger receptor class B type Ilow density lipoprotein |
| spellingShingle | Ming-Dong Wang Robert S. Kiss Vivian Franklin Heidi M. McBride Stewart C. Whitman Yves L. Marcel Different cellular traffic of LDL-cholesterol and acetylated LDL-cholesterol leads to distinct reverse cholesterol transport pathwayss⃞ Journal of Lipid Research cholesterol efflux ATP binding cassette transporter A1 ATP binding cassette transporter G1 scavenger receptor class B type I low density lipoprotein |
| title | Different cellular traffic of LDL-cholesterol and acetylated LDL-cholesterol leads to distinct reverse cholesterol transport pathwayss⃞ |
| title_full | Different cellular traffic of LDL-cholesterol and acetylated LDL-cholesterol leads to distinct reverse cholesterol transport pathwayss⃞ |
| title_fullStr | Different cellular traffic of LDL-cholesterol and acetylated LDL-cholesterol leads to distinct reverse cholesterol transport pathwayss⃞ |
| title_full_unstemmed | Different cellular traffic of LDL-cholesterol and acetylated LDL-cholesterol leads to distinct reverse cholesterol transport pathwayss⃞ |
| title_short | Different cellular traffic of LDL-cholesterol and acetylated LDL-cholesterol leads to distinct reverse cholesterol transport pathwayss⃞ |
| title_sort | different cellular traffic of ldl cholesterol and acetylated ldl cholesterol leads to distinct reverse cholesterol transport pathwayss⃞ |
| topic | cholesterol efflux ATP binding cassette transporter A1 ATP binding cassette transporter G1 scavenger receptor class B type I low density lipoprotein |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520432389 |
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