Proteomic identification and characterization of hepatic glyoxalase 1 dysregulation in non-alcoholic fatty liver disease
| Autor: | John F. Dillon, Caroline A. Evans, Naila Rabbani, David Windridge, Michael H Miller, Mark E. Weeks, Huan Wang, Paul J. Thornalley, Bernard M. Corfe, Ciarán Fisher, Francisco J. Salguero, Elaina M. Maldonado, J. Bernadette Moore, Christos Spanos, Anil Dhawan, Ernesto Oviedo-Orta, Alberto Quaglia, Petchpailin Leenutaphong, Alexandra Bermudez-Fajardo, Emer Fitzpatrick |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Proteomics medicine.medical_specialty Quantitative proteomics Biochemistry 03 medical and health sciences chemistry.chemical_compound Liver disease Glycation Internal medicine Methylglyoxal medicine lcsh:QH573-671 Molecular Biology Glyoxalase Liver injury lcsh:Cytology business.industry Research Fatty liver nutritional and metabolic diseases medicine.disease QP digestive system diseases 3. Good health 030104 developmental biology Endocrinology chemistry iTRAQ business RC Non-alcoholic fatty liver disease |
| Zdroj: | Proteome Science Proteome Science, Vol 16, Iss 1, Pp 1-16 (2018) |
| ISSN: | 1477-5956 |
| Popis: | Background Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. However, its molecular pathogenesis is incompletely characterized and clinical biomarkers remain scarce. The aims of these experiments were to identify and characterize liver protein alterations in an animal model of early, diet-related, liver injury and to assess novel candidate biomarkers in NAFLD patients. Methods Liver membrane and cytosolic protein fractions from high fat fed apolipoprotein E knockout (ApoE−/−) animals were analyzed by quantitative proteomics, utilizing isobaric tags for relative and absolute quantitation (iTRAQ) combined with nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS). Differential protein expression was confirmed independently by immunoblotting and immunohistochemistry in both murine tissue and biopsies from paediatric NAFLD patients. Candidate biomarkers were analyzed by enzyme-linked immunosorbent assay in serum from adult NAFLD patients. Results Through proteomic profiling, we identified decreased expression of hepatic glyoxalase 1 (GLO1) in a murine model. GLO1 protein expression was also found altered in tissue biopsies from paediatric NAFLD patients. In vitro experiments demonstrated that, in response to lipid loading in hepatocytes, GLO1 is first hyperacetylated then ubiquitinated and degraded, leading to an increase in reactive methylglyoxal. In a cohort of 59 biopsy-confirmed adult NAFLD patients, increased serum levels of the primary methylglyoxal-derived advanced glycation endproduct, hydroimidazolone (MG-H1) were significantly correlated with body mass index (r = 0.520, p |
| Databáze: | OpenAIRE |
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