PXD001442

PXD001442 is an original dataset announced via ProteomeXchange.

Title	Hepatic dysregulation of glyoxalase 1 in preclinical models and patients with non-alcoholic fatty liver disease
Description	Background & Aims: Although non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, aspects of its molecular pathogenesis are unknown and clinical biomarkers for early diagnosis and accurate disease staging remain scarce. The aims of these experiments were to identify and characterize liver protein alterations in an animal model of NAFLD and explore the utility of novel candidate biomarkers in NAFLD patients. Methods: Liver protein fractions were analyzed in a relative quantitative proteomic approach utilizing isobaric tags for relative and absolute quantitation (iTRAQ) labeling combined with nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS). Differential expression was confirmed independently by western blotting and immunohistochemistry, first in mouse sections and then in biopsies from paediatric NAFLD patients. Candidate serum 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 an animal model of NAFLD. GLO1 protein levels were also found reduced in tissue biopsies from pediatric NAFLD patients. In vitro experiments demonstrated that, in response to lipid-loading in hepatocytes, GLO1 is first hyper-acetylated then ubiquitinylated and degraded, leading to an increase in reactive methylglyoxal. In a cohort of 62 biopsy-confirmed adult NAFLD patients serum levels of the primary methylglyoxal-derived advanced glycated endproduct, hydroimidazolone (MG-H1) were found strongly correlated with body mass index (r=0.619, p<0.0001). Conclusions: We characterize, for the first time, the post-translational modification and regulation of GLO1 expression in response to hepatic lipid loading with functional consequences in NAFLD patients.
HostingRepository	PRIDE
AnnounceDate	2018-02-16
AnnouncementXML	Submission_2018-02-16_07:47:15.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christos Spanos
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue
Instrument	6520 Quadrupole Time-of-Flight LC/MS

Revision	Datetime	Status	ChangeLog Entry
0	2014-10-28 11:40:16	ID requested
⏵ 1	2018-02-16 07:47:15	announced

Dataset with its publication pending

curator keyword: Biological, Biomedical

submitter keyword: Glyoxalase, Liver, Mouse, Q-TOF, Quantitative proteomics, iTRAQ, nLC-MS/MS

Jennifer Bernadette Moore
contact affiliation	Faculty of Health and Medical Sciences University of Surrey
contact email	j.b.moore@surrey.ac.uk
lab head
Christos Spanos
contact affiliation	University of Surrey
contact email	spanos.christos@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD001442
     1. Label: PRIDE project
     2. Name: Hepatic dysregulation of glyoxalase 1 in preclinical models and patients with non-alcoholic fatty liver disease