| Title |
Proteomic identification and characterization of hepatic glyoxalase 1 dysregulation in non-alcoholic fatty liver disease
|
|---|---|
| Published in |
Proteome Science, February 2018
|
| DOI | 10.1186/s12953-018-0131-y |
| Pubmed ID | |
| Authors |
Christos Spanos, Elaina M. Maldonado, Ciarán P. Fisher, Petchpailin Leenutaphong, Ernesto Oviedo-Orta, David Windridge, Francisco J. Salguero, Alexandra Bermúdez-Fajardo, Mark E. Weeks, Caroline Evans, Bernard M. Corfe, Naila Rabbani, Paul J. Thornalley, Michael H. Miller, Huan Wang, John F. Dillon, Alberto Quaglia, Anil Dhawan, Emer Fitzpatrick, J. Bernadette Moore |
| Abstract |
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. 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. 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). 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. |
X Demographics
The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 3 | 60% |
| Japan | 1 | 20% |
| Unknown | 1 | 20% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 3 | 60% |
| Science communicators (journalists, bloggers, editors) | 1 | 20% |
| Members of the public | 1 | 20% |
Mendeley readers
The data shown below were compiled from readership statistics for 40 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 40 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 5 | 13% |
| Researcher | 4 | 10% |
| Student > Postgraduate | 4 | 10% |
| Professor > Associate Professor | 4 | 10% |
| Student > Bachelor | 3 | 8% |
| Other | 8 | 20% |
| Unknown | 12 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 5 | 13% |
| Biochemistry, Genetics and Molecular Biology | 5 | 13% |
| Medicine and Dentistry | 5 | 13% |
| Engineering | 3 | 8% |
| Nursing and Health Professions | 2 | 5% |
| Other | 6 | 15% |
| Unknown | 14 | 35% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 April 2019.
All research outputs
#7,240,217
of 23,753,899 outputs
Outputs from Proteome Science
#35
of 196 outputs
Outputs of similar age
#147,890
of 449,645 outputs
Outputs of similar age from Proteome Science
#2
of 3 outputs
Altmetric has tracked 23,753,899 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 196 research outputs from this source. They receive a mean Attention Score of 2.8. This one has done well, scoring higher than 82% of its peers.
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