title: Quantitative toxicoproteomic analysis of zebrafish embryos exposed to a retinoid X receptor antagonist UVI3003.
abstract: Retinoid X receptor (RXR) antagonists, including some environmental endocrine disruptors, have a teratogenic effect on vertebrate embryos. To investigate the toxicological mechanism on the protein expression level, a quantitative proteomic study was conducted to analyze the proteome alterations of zebrafish (Danio rerio) embryos exposed to gradient concentrations of a representative RXR antagonist UVI3003. Using isobaric Tags for Relative and Absolute Quantitation (iTRAQ) labeling coupled nano high-performance liquid chromatography-tandem mass spectrometry (nano HPLC-MS/MS), in total 6592 proteins were identified, among which 195 proteins were found to be differentially expressed by more than a two-fold change in exposed groups compared with the control. Gene ontology analysis showed that these differential proteins were mostly involved in anatomical structure development, biosynthetic process, ion binding and oxidoreductase activity. Moreover, the biological pathways of translation, lipoprotein metabolism, cell survival and gluconeogenesis were intensively inhibited after exposure. Some significantly downregulated proteins such as apolipoprotein A-I and vitellogenin and upregulated proteins such as calcium activated nucleotidase 1b, glutathione S-transferase and glucose 6-dehydrogenases showed a strong dose-dependent response. The results provided new insight into the molecular details of RXR antagonist-induced teratogenicity and added novel information of pathways and potential biomarkers for evaluation of RXR interfering activity.
authors.affiliation: State Key Laboratory of Estuarine and Coastal Research, East China Normal University, 3663 Zhongshan (N) Road, Shanghai, 200062, China.|Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, One Illini Drive, Peoria, IL, 61605, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Asia Pacific Application Support Center, AB SCIEX, 888 Tianlin Road, Shanghai, 200233, China.
authors.forename: Jianlan
authors.initials: J
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Estuarine and Coastal Research, East China Normal University, 3663 Zhongshan (N) Road, Shanghai, 200062, China.
authors.forename: Huahong
authors.initials: H
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Estuarine and Coastal Research, East China Normal University, 3663 Zhongshan (N) Road, Shanghai, 200062, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Estuarine and Coastal Research, East China Normal University, 3663 Zhongshan (N) Road, Shanghai, 200062, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xin
authors.affiliation: State Key Laboratory of Estuarine and Coastal Research, East China Normal University, 3663 Zhongshan (N) Road, Shanghai, 200062, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Estuarine and Coastal Research, East China Normal University, 3663 Zhongshan (N) Road, Shanghai, 200062, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Asia Pacific Application Support Center, AB SCIEX, 888 Tianlin Road, Shanghai, 200233, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Luo
authors.affiliation: Asia Pacific Application Support Center, AB SCIEX, 888 Tianlin Road, Shanghai, 200233, China.
authors.forename: Wenhai
authors.initials: W
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Estuarine and Coastal Research, East China Normal University, 3663 Zhongshan (N) Road, Shanghai, 200062, China.
authors.forename: Daoji
authors.initials: D
authors.lastname: Li
authors.affiliation: State Key Laboratory of Estuarine and Coastal Research, East China Normal University, 3663 Zhongshan (N) Road, Shanghai, 200062, China.
authors.forename: Junliang
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D003373:Coumaric Acids / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D063990:Gene Ontology; D008297:Male; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D047488:Retinoid X Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D013764:Tetrahydronaphthalenes / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism
chemical_list: D003373:Coumaric Acids; D020543:Proteome; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes; C525131:UVI 3003
keywords: RXR antagonist; iTRAQ labeling; nano HPLC-MS/MS; toxicoproteomics; zebrafish embryo