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http://hdl.handle.net/2445/210980
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DC Field | Value | Language |
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dc.contributor.author | Mendoza Barberá, Elena de | - |
dc.contributor.author | Julve, Josep | - |
dc.contributor.author | Nilsson, Stefan K. | - |
dc.contributor.author | Lookene, Aivar | - |
dc.contributor.author | Martín Campos, Jesús M. | - |
dc.contributor.author | Roig, Rosa | - |
dc.contributor.author | Lechuga Sancho, Alfonso M. | - |
dc.contributor.author | Sloan, John H. | - |
dc.contributor.author | Fuentes Prior, Pablo | - |
dc.contributor.author | Blanco Vaca, Francisco | - |
dc.date.accessioned | 2024-05-07T08:36:24Z | - |
dc.date.available | 2024-05-07T08:36:24Z | - |
dc.date.issued | 2013-01-10 | - |
dc.identifier.issn | 0022-2275 | - |
dc.identifier.uri | http://hdl.handle.net/2445/210980 | - |
dc.description.abstract | <p>During the diagnosis of three unrelated patients with severe hypertriglyceridemia, three APOA5 mutations [p.(Ser232_Leu235)del, p.Leu253Pro, and p.Asp332ValfsX4] were found without evidence of concomitant LPL, APOC2, or GPIHBP1 mutations. The molecular mechanisms by which APOA5 mutations result in severe hypertriglyceridemia remain poorly understood, and the functional impairment/s induced by these specific mutations was not obvious. Therefore, we performed a thorough structural and functional analysis that included follow-up of patients and their closest relatives, measurement of apoA-V serum concentrations, and sequencing of the APOA5 gene in 200 nonhyperlipidemic controls. Further, we cloned, overexpressed, and purified both wild-type and mutant apoA-V variants and characterized their capacity to activate LPL. The interactions of recombinant wild-type and mutated apoA-V variants with liposomes of different composition, heparin, LRP1, sortilin, and SorLA/LR11 were also analyzed. Finally, to explore the possible structural consequences of these mutations, we developed a three-dimensional model of full-length, lipid-free human apoA-V. A complex, wide array of impairments was found in each of the three mutants, suggesting that the specific residues affected are critical structural determinants for apoA-V function in lipoprotein metabolism and, therefore, that these APOA5 mutations are a direct cause of hypertriglyceridemia.</p> | - |
dc.format.extent | 13 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | American Society for Biochemistry and Molecular Biology | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1194/jlr.M031195 | - |
dc.relation.ispartof | Journal of Lipid Research, 2013, vol. 54, num.3, p. 649-661 | - |
dc.relation.uri | https://doi.org/10.1194/jlr.M031195 | - |
dc.rights | (c) American Society for Biochemistry and Molecular Biology, 2013 | - |
dc.source | Articles publicats en revistes (Biologia, Sanitat i Medi Ambient) | - |
dc.subject.classification | Expressió gènica | - |
dc.subject.classification | Malalties cardiovasculars | - |
dc.subject.classification | Triglicèrids | - |
dc.subject.other | Gene expression | - |
dc.subject.other | Cardiovascular diseases | - |
dc.subject.other | Triglycerides | - |
dc.title | Structural and functional analysis of APOA5 mutations identified in patients with severe hypertriglyceridemia | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 722607 | - |
dc.date.updated | 2024-05-07T08:36:29Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Biologia, Sanitat i Medi Ambient) |
Files in This Item:
File | Description | Size | Format | |
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249704.pdf | 1.15 MB | Adobe PDF | View/Open |
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