Families of Nuclear Receptors in Vertebrate Models: Characteristic and Comparative Toxicological Perspective

Zhao, Yanbin; Zhang, Kun; Giesy, John P.; Hu, Jianying

doi:10.1038/srep08554

Cited by 60 publications

(49 citation statements)

References 45 publications

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“…Arthropod NRs are fewer in number and less divergent than NRs found in vertebrates, particularly amongst the NR3 subfamily which has only a single representative in arthropods compared to 9 in mammals and in up to 15 in fish [85, 86]. Despite this, some crustacean NRs have been shown to be vulnerable to modulation by xenobiotics.…”

Section: Resultsmentioning

confidence: 99%

De novo assembly and analysis of changes in the protein-coding transcriptome of the freshwater shrimp Paratya australiensis (Decapoda: Atyidae) in response to acid sulfate drainage water

2016

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BackgroundThe atyid shrimp Paratya australiensis occurs in surface freshwater habitats throughout eastern Australia and has been used to study the ecotoxicology of contaminants such as pesticides and metals. The acidification of surface water that can occur after acid sulfate material in soils and sediments is oxidised and subsequently re-wetted is a serious environmental issue in coastal regions and inland riverine floodplains worldwide. Solubilisation of soil-associated minerals can result in high waterborne concentrations of mineral salts and dissolved metals, which together with low pH represent a potential threat to aquatic ecosystems in affected regions. The aims of the present study were to gain insight into stress responses induced by exposure to acid drainage water (ADW) in P. australiensis by determining changes in the abundance of protein-coding transcripts and to generate a comprehensive transcriptomic resource to facilitate further research into gene regulation or protein structure and function in this species. Adult P. australiensis were exposed for 24 h to undiluted ADW, 50 % ADW diluted in river water, or to river water as control, and high-throughput mRNA sequencing (RNA-Seq) conducted on whole-body tissues. A reference transcriptome was generated using de novo assembly and putative protein-coding regions were identified and annotated. Changes in transcript abundance in response to ADW exposure were determined by aligning reads to the reference transcriptome and quantifying coverage.ResultsA high proportion of arthropod benchmarking universal single-copy orthologues were present in the reference transcriptome. Functions associated with cuticle biosynthesis and oxidative stress were significantly enriched in the lists of transcripts exhibiting differential abundance in either direction after exposure to 50 % or 100 % ADW. Transcripts involved in osmoregulation exhibited decreased abundance following exposure to ADW. The transcriptome contained full-length coding sequences for numerous proteins known to be involved in environmental response pathways, including two putative metallothioneins, four glutathione peroxidases and 19 nuclear receptors.ConclusionsThe results of the present study provide insight into stress response pathways induced in crustaceans by short-term exposure to multiple stressors present in ADW such as low pH, high salinity and dissolved metals, and represent a resource for future toxicogenomics and protein functional studies in P. australiensis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3208-y) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

De novo assembly and analysis of changes in the protein-coding transcriptome of the freshwater shrimp Paratya australiensis (Decapoda: Atyidae) in response to acid sulfate drainage water

2016

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“…The zebrafish nPR comprises of 617 amino acids with high homology to other vertebrates. The homology between fish PR is high, in particular in the ligand binding domain (Zhao et al, 2015a). The zebrafish PR contains five domains, characteristic of nuclear steroid receptors (Hanna et al, 2010;Chen et al, 2010).…”

Section: Nuclear Progesterone Receptorsmentioning

confidence: 99%

Progestins as endocrine disrupters in aquatic ecosystems: Concentrations, effects and risk assessment

Fent

2015

Environment International

200

129

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“…CAR ligands are species-specific which can be attributed to limited conservation of CAR’s ligand binding domain. For example the ligand binding domains of human and murine CAR are only 75% conserved [136]. …”

Section: Constitutive Androstane Receptormentioning

confidence: 99%

Nuclear receptors and nonalcoholic fatty liver disease

Cave

Clair

Hardesty

et al. 2016

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

235

204

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Nuclear receptors are transcription factors which sense changing environmental or hormonal signals and effect transcriptional changes to regulate core life functions including growth, development, and reproduction. To support this function, following ligand-activation by xenobiotics, members of subfamily 1 nuclear receptors (NR1s) may heterodimerize with the retinoid X receptor (RXR) to regulate transcription of genes involved in energy and xenobiotic metabolism and inflammation. Several of these receptors including the peroxisome proliferator-activated receptors (PPARs), the pregnane and xenobiotic receptor (PXR), the constitutive androstane receptor (CAR), the liver X receptor (LXR) and the farnesoid X receptor (FXR) are key regulators of the gut:liver:adipose axis and serve to coordinate metabolic responses across organ systems between the fed and fasting states. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and may progress to cirrhosis and even hepatocellular carcinoma. NAFLD is associated with inappropriate nuclear receptor function and perturbations along the gut:liver:adipose axis including obesity, increased intestinal permeability with systemic inflammation, abnormal hepatic lipid metabolism, and insulin resistance. Environmental chemicals may compound the problem by directly interacting with nuclear receptors leading to metabolic confusion and the inability to differentiate fed from fasting conditions. This review focuses on the impact of nuclear receptors in the pathogenesis and treatment of NAFLD. Clinical trials including PIVENS and FLINT demonstrate that nuclear receptor targeted therapies may lead to the paradoxical dissociation of steatosis, inflammation, fibrosis, insulin resistance, dyslipidemia and obesity. Novel strategies currently under development (including tissue-specific ligands and dual receptor agonists) may be required to separate the beneficial effects of nuclear receptor activation from unwanted metabolic side effects. The impact of nuclear receptor crosstalk in NAFLD is likely to be profound, but requires further elucidation. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie.

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Families of Nuclear Receptors in Vertebrate Models: Characteristic and Comparative Toxicological Perspective

Cited by 60 publications

References 45 publications

De novo assembly and analysis of changes in the protein-coding transcriptome of the freshwater shrimp Paratya australiensis (Decapoda: Atyidae) in response to acid sulfate drainage water

De novo assembly and analysis of changes in the protein-coding transcriptome of the freshwater shrimp Paratya australiensis (Decapoda: Atyidae) in response to acid sulfate drainage water

Progestins as endocrine disrupters in aquatic ecosystems: Concentrations, effects and risk assessment

Nuclear receptors and nonalcoholic fatty liver disease

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