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Proteomic identification and characterization of hepatic glyoxalase 1 dysregulation in non-alcoholic fatty liver disease
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(2018) Proteomic identification and characterization of hepatic glyoxalase 1 dysregulation in non-alcoholic fatty liver disease. Proteome Science, 16 (1). 4. doi:10.1186/s12953-018-0131-y ISSN 1477-5956.
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Official URL: http://dx.doi.org/10.1186/s12953-018-0131-y
Abstract
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 < 0.0001).
Conclusion:
Collectively these results demonstrate the dysregulation of GLO1 in NAFLD and implicate the acetylation-ubquitination degradation pathway as the functional mechanism. Further investigation of the role of GLO1 in the molecular pathogenesis of NAFLD is warranted.
Item Type: | Journal Article | ||||||||||||||||||
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Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Fatty liver -- Pathogenesis, Liver -- Diseases -- Pathogenesis, Biochemical markers, Proteomics, Glyoxalase, Glyoxal | ||||||||||||||||||
Journal or Publication Title: | Proteome Science | ||||||||||||||||||
Publisher: | BioMed Central Ltd. | ||||||||||||||||||
ISSN: | 1477-5956 | ||||||||||||||||||
Official Date: | 14 February 2018 | ||||||||||||||||||
Dates: |
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Volume: | 16 | ||||||||||||||||||
Number: | 1 | ||||||||||||||||||
Article Number: | 4 | ||||||||||||||||||
DOI: | 10.1186/s12953-018-0131-y | ||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||
Date of first compliant deposit: | 2 August 2018 | ||||||||||||||||||
Date of first compliant Open Access: | 2 August 2018 | ||||||||||||||||||
RIOXX Funder/Project Grant: |
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