BackgroundNon-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.MethodsLiver 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.ResultsThrough 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).ConclusionCollectively 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.Electronic supplementary materialThe online version of this article (10.1186/s12953-018-0131-y) contains supplementary material, which is available to authorized users.
D scandens ( Derris scandens Benth.) and E scaber ( Elephantopus scaber Linn.) contain flavonoids and phenolic acids, which have antitumor activity in various cancer cell lines. Oral cancer is among the most common cancers in Southeast Asia, and the survival rate remains low. Thus, this study screened 2 ethanolic plant extracts for cytotoxicity on the oral human squamous carcinoma cell line (HSC-2), and compared the mechanisms of action. Extracts of D scandens and E scaber showed cytotoxicity against HSC-2 cells in a dose-dependent manner. Observation of nuclear morphology by Hoechst 33342 staining revealed chromatin condensation. Apoptosis was confirmed by Annexin V-FITC staining and cell sorting (fluorescence-activated cell sorting) analysis. We demonstrated that cancer apoptosis was accompanied by changes in the expression of procaspase 3 and that D scandens-mediated apoptosis in HSC-2 cells was potentiated by protein kinase B (Akt) and B-cell lymphoma-2 (Bcl-2), while E scaber apoptosis was mediated by mitogen-activated protein kinase (MAPK) pathways, involving stress-activated protein kinases/jun amino-terminal kinase (SAPK/JNK) and p38-MAPK. Further investigation into targets for apoptosis induction by these plant extracts may have potential in oral cancer therapy.
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