The cellular degradation of the low density lipoprotein receptor and its ligand

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dc.contributor.advisorCoetzee, G Aen_ZA
dc.contributor.authorCasciola, Livia Angela Flaviaen_ZA
dc.date.accessioned2018-02-01T13:32:37Z
dc.date.available2018-02-01T13:32:37Z
dc.date.issued1987en_ZA
dc.description.abstractThe cellular degradation of the low density lipoprotein (LDL) receptor, and its ligand, LDL, were investigated in order to clarify certain mechanistic aspects of these important processes. Long-term lymphoblastoid cell lines and cultured human skin fibroblasts were used to examine the fate of ¹²⁵I-LDL subsequent to its uptake via receptor-mediated endocytosis. In both cases, binding activity was saturable, depended on the presence of calcium ions in the medium, and was calculated to have an equilibrium dissociation constant at 4ᵒC of 2 μg ¹²⁵I-LDL/ml. No high-affinity binding was detected when the ligand was modified by acetylation. After incubating the monolayers at 37°C LDL/LDL receptor complexes were internalized, and the receptors were recycled back to the surface within about 10 minutes. Apolipo-protein B in the LDL particles was largely degraded to the amino acid level: chloroquine, a lysosomotropic agent, inhibited the formation of the ¹²⁵I-LDL degradation products. Cells obtained from a number of heterozygous and homozygous familial hypercholesterolemic patients, as expected, bound markedly reduced amounts of ligand. The half-life of ¹²⁵I-LDL was measured after it had been introduced into cultured fibroblasts by one of the following processes: (i) uptake via receptor-mediated endocytosis in human skin fibroblasts with normal LDL receptors, or (ii) incorporation via scrape-loading into fibroblasts defective in LDL receptor content. The half-lives obtained were about 1 hour and 50 hours, respectively, indicating that efficient degradation of LDL occurred only when it was deIivered to lysosomes via receptor-mediated endocytosis.en_ZA
dc.identifier.apacitationCasciola, L. A. F. (1987). <i>The cellular degradation of the low density lipoprotein receptor and its ligand</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Medical Biochemistry & Structural Biology. Retrieved from http://hdl.handle.net/11427/27207en_ZA
dc.identifier.chicagocitationCasciola, Livia Angela Flavia. <i>"The cellular degradation of the low density lipoprotein receptor and its ligand."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Medical Biochemistry & Structural Biology, 1987. http://hdl.handle.net/11427/27207en_ZA
dc.identifier.citationCasciola, L. 1987. The cellular degradation of the low density lipoprotein receptor and its ligand. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Casciola, Livia Angela Flavia AB - The cellular degradation of the low density lipoprotein (LDL) receptor, and its ligand, LDL, were investigated in order to clarify certain mechanistic aspects of these important processes. Long-term lymphoblastoid cell lines and cultured human skin fibroblasts were used to examine the fate of ¹²⁵I-LDL subsequent to its uptake via receptor-mediated endocytosis. In both cases, binding activity was saturable, depended on the presence of calcium ions in the medium, and was calculated to have an equilibrium dissociation constant at 4ᵒC of 2 μg ¹²⁵I-LDL/ml. No high-affinity binding was detected when the ligand was modified by acetylation. After incubating the monolayers at 37°C LDL/LDL receptor complexes were internalized, and the receptors were recycled back to the surface within about 10 minutes. Apolipo-protein B in the LDL particles was largely degraded to the amino acid level: chloroquine, a lysosomotropic agent, inhibited the formation of the ¹²⁵I-LDL degradation products. Cells obtained from a number of heterozygous and homozygous familial hypercholesterolemic patients, as expected, bound markedly reduced amounts of ligand. The half-life of ¹²⁵I-LDL was measured after it had been introduced into cultured fibroblasts by one of the following processes: (i) uptake via receptor-mediated endocytosis in human skin fibroblasts with normal LDL receptors, or (ii) incorporation via scrape-loading into fibroblasts defective in LDL receptor content. The half-lives obtained were about 1 hour and 50 hours, respectively, indicating that efficient degradation of LDL occurred only when it was deIivered to lysosomes via receptor-mediated endocytosis. DA - 1987 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 1987 T1 - The cellular degradation of the low density lipoprotein receptor and its ligand TI - The cellular degradation of the low density lipoprotein receptor and its ligand UR - http://hdl.handle.net/11427/27207 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/27207
dc.identifier.vancouvercitationCasciola LAF. The cellular degradation of the low density lipoprotein receptor and its ligand. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Medical Biochemistry & Structural Biology, 1987 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/27207en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDivision of Medical Biochemistry and Structural Biology
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherCell receptorsen_ZA
dc.subject.otherLipoproteinsen_ZA
dc.subject.otherHistocytochemistryen_ZA
dc.subject.otherLigandsen_ZA
dc.subject.otherLipoproteins, LDLen_ZA
dc.subject.otherReceptors, LDLen_ZA
dc.titleThe cellular degradation of the low density lipoprotein receptor and its liganden_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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