Identification and Characterization of Caveolins in Mouse Macrophages
dc.contributor.advisor | Dory, Lad | |
dc.contributor.committeeMember | Basu, Alakananda | |
dc.contributor.committeeMember | McConathy, Walter | |
dc.creator | Gargalovic, Peter | |
dc.date.accessioned | 2019-08-22T19:42:45Z | |
dc.date.available | 2019-08-22T19:42:45Z | |
dc.date.issued | 2002-12-01 | |
dc.date.submitted | 2013-08-06T13:54:06-07:00 | |
dc.description.abstract | Peter Gargalovic, Identification and Characterization of Caveolins in Mouse Macrophages. Doctor of Philosophy (Biochemistry and Molecular Biology), December 2002, 206 pp., 3 tables, 41 illustrations, references, 296 titles. The understanding of the mechanisms which control macrophage-lipid management, and their accumulation in atherosclerotic lesions, is of significant importance. Caveolins are proteins associated with cholesterol-rich membrane domains and are intimately linked to the regulation of lipid metabolism and transport. The expression and function of caveolin proteins in three macrophage cell types: thioglycollate-elicited mouse peritoneal macrophages, resident mouse peritoneal macrophages and the J774 macrophage cell line. Data in this work establish that the primary macrophages express caveolin-1 and -2, while J774 cells express only caveolin-2. Immunofluorescence microscopy studies indicate that caveolins in primary macrophages do not colocalize, with caveolin-1 being present on the cell surface and cavelon-2 in the Golgi compartment. Analysis of macrophages also showed that caveolin-1, but not caveolin-2, is present in detergent insoluble lipid raft membranes. While caveolin expression in macrophages is not regulated by sterols, both caveolin isoforms can be secreted from cholesterol-loaded macrophages in the presence of high-density lipoprotein (HDL). Secreted caveolins are part of the complex that has a density similar to HDL, which suggests their association with HDL and potentially a role in HDL-mediated reverse cholesterol transport. The examination of caveolin expression in macrophages shows that caveolin-1, but not caveolin-2 expression is highly upregulated by agents that induce apoptosis in these cells. Induction of caveolin-1 expression precedes DNA fragmentation, is independent of caspase activation, and correlates with the exposure of phosphatidylserine on the cell surface. Importantly, immunofluorescence analysis determined that caveolin-1 in lipid rafts colocalizes extensively with phosphatidylserine present on the surface of apoptotic cells. This study thus identifies caveolin-1 as a specific and early marker of the macrophage apoptotic phenotype. Findings here strongly implicate the involvement of caveolin-1 and lipid rafts in the changes of plasma membrane lipid composition as well as involvement in efficient clearance of apoptotic cells by a phosphatidylserine-mediated mechanism. | |
dc.format.mimetype | application/pdf | |
dc.identifier.uri | https://hdl.handle.net/20.500.12503/26791 | |
dc.language.iso | en | |
dc.provenance.legacyDownloads | 20 | |
dc.subject | Cardiovascular System | |
dc.subject | Cell and Developmental Biology | |
dc.subject | Cell Biology | |
dc.subject | Cells | |
dc.subject | Comparative and Laboratory Animal Medicine | |
dc.subject | Genetic Phenomena | |
dc.subject | Genetics | |
dc.subject | Genetics and Genomics | |
dc.subject | Life Sciences | |
dc.subject | Lipids | |
dc.subject | Medical Cell Biology | |
dc.subject | Medical Molecular Biology | |
dc.subject | Medical Sciences | |
dc.subject | Medicine and Health Sciences | |
dc.subject | Microbiology | |
dc.subject | Other Cell and Developmental Biology | |
dc.subject | Other Genetics and Genomics | |
dc.subject | Veterinary Medicine | |
dc.subject | Mouse macrophage | |
dc.subject | macrophage-lipid management | |
dc.subject | caveolins | |
dc.subject | cholesterol | |
dc.subject | phosphatidylserine | |
dc.subject | apoptotic phenotype | |
dc.subject | high-density lipoprotein | |
dc.title | Identification and Characterization of Caveolins in Mouse Macrophages | |
dc.type | Dissertation | |
dc.type.material | text | |
thesis.degree.department | Graduate School of Biomedical Sciences | |
thesis.degree.discipline | Biochemistry and Molecular Biology | |
thesis.degree.grantor | University of North Texas Health Science Center at Fort Worth | |
thesis.degree.name | Doctor of Philosophy |
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