Reduced CETP glycosylation and activity in patients with homozygous B4GALT1 mutations
| Autor: | Johannes H.M. Levels, Geesje M. Dallinga-Thie, Cleo L. Crunelle, Maryse Guerin, Sacha D. Kuil, Erik S.G. Stroes, Alinda W. M. Schimmel, Lars E. Larsen, Jan Albert Kuivenhoven, Lubna Ali, Vassiliki Konstantopoulou, Marjolein A.W. van den Boogert, Adriaan G. Holleboom, Dirk Lefeber |
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| Přispěvatelé: | Center for Liver, Digestive and Metabolic Diseases (CLDM), Lifestyle Medicine (LM), Graduate School, ACS - Atherosclerosis & ischemic syndromes, Amsterdam Cardiovascular Sciences, Amsterdam Gastroenterology Endocrinology Metabolism, APH - Global Health, APH - Methodology, APH - Quality of Care, Experimental Vascular Medicine, ACS - Diabetes & metabolism, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, Vascular Medicine, VU University Medical Center [Amsterdam], Vrije Universiteit Brussel (VUB), Radboud University Medical Center [Nijmegen], Medizinische Universität Wien = Medical University of Vienna, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University Medical Center Groningen [Groningen] (UMCG), Faculty of Medicine and Pharmacy, Psychiatry, Applied Mechanics, Robotics & Multibody Mechanics Research Group |
| Rok vydání: | 2019 |
| Předmět: |
Male
Endothelial lipase B4GALT1 chemistry.chemical_compound Congenital Disorders of Glycosylation Genetics(clinical) Child Genetics (clinical) RISK 0303 health sciences PLASMA biology medicine.diagnostic_test Protein galactosylation CHOLESTEROL Homozygote 030305 genetics & heredity [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] Galactosyltransferases 3. Good health DEFICIENCY Child Preschool Female Original Article lipids (amino acids peptides and proteins) congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Glycosylation Adolescent glycosylation HDL CONGENITAL DISORDERS LDL lipids LIPOPROTEINS 03 medical and health sciences Western blot Internal medicine CETP Cholesterylester transfer protein Genetics medicine Humans 030304 developmental biology Cholesterol Cholesterol HDL Infant Lipid metabolism Cholesterol LDL Original Articles Cholesterol Ester Transfer Proteins carbohydrates (lipids) ENDOTHELIAL LIPASE Endocrinology chemistry Case-Control Studies Mutation biology.protein CDG GOLGI HOMEOSTASIS Lipoprotein |
| Zdroj: | Journal of Inherited Metabolic Disease, 43(3), 611-617. SPRINGER Journal of Inherited Metabolic Disease Journal of inherited metabolic disease, 43(3), 611-617. Springer Netherlands Journal of Inherited Metabolic Disease, 43, 3, pp. 611-617 Journal of Inherited Metabolic Disease, Springer Verlag, 2020, 43 (3), pp.611-617. ⟨10.1002/jimd.12200⟩ Journal of Inherited Metabolic Disease, 43, 611-617 |
| ISSN: | 1573-2665 0141-8955 |
| Popis: | Contains fulltext : 220538.pdf (Publisher’s version ) (Open Access) The importance of protein glycosylation in regulating lipid metabolism is becoming increasingly apparent. We set out to further investigate this by studying the effects of defective glycosylation on plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation. We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls. B4GALT1-CDG patients have significantly lowered non-high density lipoprotein cholesterol (HDL-c) and total cholesterol to HDL-c ratio compared with controls and larger HDL particles. Plasma CETP was hypoglycosylated and less active in B4GALT1-CDG patients compared to matched controls. Our study provides insight into the role of protein glycosylation in human lipoprotein homeostasis. The hypogalactosylated, hypo-active CETP found in patients with B4GALT1-CDG indicates a role of protein galactosylation in regulating plasma HDL and LDL. Patients with B4GALT1-CDG have large HDL particles probably due to hypogalactosylated, hypo-active CETP. |
| Databáze: | OpenAIRE |
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