Functional characterisation of peroxisomal β-oxidation disorders in fibroblasts using lipidomics
| Autor: | Frédéric M. Vaz, Angela C. M. Luyf, Ronald J.A. Wanders, Sacha Ferdinandusse, Antoine H. C. van Kampen, Katharina Herzog, Mia L. Pras-Raves, Hans R. Waterham, Martin A. T. Vervaart |
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| Přispěvatelé: | Biosystems Data Analysis (SILS, FNWI), Amsterdam Reproduction & Development (AR&D), Graduate School, ARD - Amsterdam Reproduction and Development, APH - Methodology, Laboratory Genetic Metabolic Diseases, APH - Personalized Medicine, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ANS - Amsterdam Neuroscience, ACS - Amsterdam Cardiovascular Sciences, Epidemiology and Data Science, Paediatric Metabolic Diseases |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Very long-chain fatty acids Plasmalogens Phospholipid Biology Mass Spectrometry Peroxisomal Disorders 03 medical and health sciences chemistry.chemical_compound Peroxisomal disorder Lipidomics Peroxisomes Genetics medicine Humans Metabolomics Cells Cultured Chromatography High Pressure Liquid Phospholipids Genetics (clinical) Skin chemistry.chemical_classification Peroxisomal matrix Fatty Acids Fatty acid Fibroblasts Lipidome Peroxisome Lipid Metabolism medicine.disease Lipids 030104 developmental biology chemistry Biochemistry Case-Control Studies β-oxidation ACOX1 Oxidation-Reduction |
| Zdroj: | Journal of inherited metabolic disease, 41(3), 479-487. Springer Netherlands Journal of Inherited Metabolic Disease, 41(3), 479-487. Springer Netherlands Journal of inherited metabolic disease, 41(3). Springer Netherlands Journal of Inherited Metabolic Disease |
| ISSN: | 0141-8955 |
| DOI: | 10.1007/s10545-017-0076-9 |
| Popis: | Peroxisomes play an important role in a variety of metabolic pathways, including the α- and β-oxidation of fatty acids, and the biosynthesis of ether phospholipids. Single peroxisomal enzyme deficiencies (PEDs) are a group of peroxisomal disorders in which either a peroxisomal matrix enzyme or a peroxisomal membrane transporter protein is deficient. To investigate the functional consequences of specific enzyme deficiencies on the lipidome, we performed lipidomics using cultured skin fibroblasts with different defects in the β-oxidation of very long-chain fatty acids, including ABCD1- (ALD), acyl-CoA oxidase 1 (ACOX1)-, D-bifunctional protein (DBP)-, and acyl-CoA binding domain containing protein 5 (ACBD5)-deficient cell lines. Ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry revealed characteristic changes in the phospholipid composition in fibroblasts with different fatty acid β-oxidation defects. Remarkably, we found that ether phospholipids, including plasmalogens, were decreased. We defined specific phospholipid ratios reflecting the different enzyme defects, which can be used to discriminate the PED fibroblasts from healthy control cells. Electronic supplementary material The online version of this article (doi:10.1007/s10545-017-0076-9) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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