Proteomic identification and characterization of hepatic glyoxalase 1 dysregulation in non-alcoholic fatty liver disease

Article

Spanos, C., Maldonado, E., Fisher, C., Leenutaphong, P., Oviedo-Orta, E., Windridge, D. and Salguero, F. 2018. Proteomic identification and characterization of hepatic glyoxalase 1 dysregulation in non-alcoholic fatty liver disease. Proteome Science. 16 (1). https://doi.org/10.1186/s12953-018-0131-y
TypeArticle
TitleProteomic identification and characterization of hepatic glyoxalase 1 dysregulation in non-alcoholic fatty liver disease
AuthorsSpanos, C., Maldonado, E., Fisher, C., Leenutaphong, P., Oviedo-Orta, E., Windridge, D. and Salguero, F.
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.
Keywords: Non-alcoholic fatty liver disease, Glyoxalase, Methylglyoxal, Proteomics, iTRAQ

KeywordsNon-alcoholic fatty liver disease; Glyoxalase; Methylglyoxal ; Proteomics; iTRAQ
PublisherBioMed Central
JournalProteome Science
ISSN1477-5956
Publication dates
Online14 Feb 2018
Print14 Feb 2018
Publication process dates
Deposited27 Feb 2018
Accepted04 Feb 2018
Output statusPublished
Publisher's version
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Copyright Statement

© The Author(s). 2018

Digital Object Identifier (DOI)https://doi.org/10.1186/s12953-018-0131-y
PubMed ID29456458
PubMed Central ID5813374
Web of Science identifierWOS:000425756600001
LanguageEnglish
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Yan, F., Kittler, J., Windridge, D., Christmas, W., Mikolajczyk, K., Cox, S. and Huang, Q. 2014. Automatic annotation of tennis games: an integration of audio, vision, and learning. Image and Vision Computing. 32 (11), pp. 896-903. https://doi.org/10.1016/j.imavis.2014.08.004
A kernel-based framework for medical big-data analytics
Windridge, D. and Bober, M. 2014. A kernel-based framework for medical big-data analytics. in: Interactive Knowledge Discovery and Data Mining in Biomedical Informatics: State-of-the-Art and Future Challenges Springer. pp. 197-208
High throughput screening for mammography using a human-computer interface with rapid serial visual presentation (RSVP)
Abbey, C., Hope, C., Sterr, A., Elangovan, P., Geades, N., Windridge, D., Young, K., Wells, K. and Mello-Thoms, C. 2013. High throughput screening for mammography using a human-computer interface with rapid serial visual presentation (RSVP). SPIE Proceedings Vol. 8673. https://doi.org/10.1117/12.2007557
Looking to score: the dissociation of goal influence on eye movement and meta-attentional allocation in a complex dynamic natural scene
Taya, S., Windridge, D. and Osman, M. 2012. Looking to score: the dissociation of goal influence on eye movement and meta-attentional allocation in a complex dynamic natural scene. PLoS ONE. 7 (6). https://doi.org/10.1371/journal.pone.0039060
Addressing missing values in kernel-based multimodal biometric fusion using neutral point substitution
Poh, N., Windridge, D., Mottl, V., Tatarchuk, A. and Eliseyev, A. 2010. Addressing missing values in kernel-based multimodal biometric fusion using neutral point substitution. IEEE Transactions on Information Forensics and Security. 5 (3), pp. 461-469. https://doi.org/10.1109/TIFS.2010.2053535