A Review of the Functional Roles of the Zebrafish Aryl Hydrocarbon Receptors

Shankar, Prarthana; Dasgupta, Subham; Hahn, Mark E.; Tanguay, Robert L.

doi:10.1093/toxsci/kfaa143

Cited by 33 publications

(17 citation statements)

References 222 publications

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“…Orthologs of the mammalian AhR are present in sharks (Chondrichthyes), gar fish (Holostei), and sturgeons (Chondrostei), but they are absent in many teleost species. An exception is the zebrafish, where the isoform AhR1α appears to be an ortholog of the mammalian AhR [20,115]. The AhRs of teleosts can be grouped into two clades (AhR1, AhR2), with each clade often being present as duplicate pairs, i.e., AhR1a-AhR2a and AhR1b-AhR2b [20,116,117].…”

Section: The Ahr In Fishmentioning

confidence: 99%

“…The essential characteristics of AhR signaling in mammals are conserved in fish, and the piscine AhRs show similar-although not identical-ligand binding preferences as the mammalian AhR, with high affinity binding of TCDD, non-ortho-substituted PCBs, and a series of PAHs [21,120,121]. The AhRs in fish have been studied intensively with respect to their role in regulating enzymes of xenobiotic metabolism and in mediating the toxicity of HAHs and PAHs, in particular their developmental and reproductive toxicity in fish [23,24,115,[122][123][124][125]. The immune system as a potential target system of AhR-activating contaminants in fish, however, has attracted surprisingly little research attention.…”

Section: The Ahr In Fishmentioning

confidence: 99%

See 1 more Smart Citation

Immunotoxicity of Xenobiotics in Fish: A Role for the Aryl Hydrocarbon Receptor (AhR)?

Segner

Bailey²,

Tafalla³

et al. 2021

IJMS

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The impact of anthropogenic contaminants on the immune system of fishes is an issue of growing concern. An important xenobiotic receptor that mediates effects of chemicals, such as halogenated aromatic hydrocarbons (HAHs) and polyaromatic hydrocarbons (PAHs), is the aryl hydrocarbon receptor (AhR). Fish toxicological research has focused on the role of this receptor in xenobiotic biotransformation as well as in causing developmental, cardiac, and reproductive toxicity. However, biomedical research has unraveled an important physiological role of the AhR in the immune system, what suggests that this receptor could be involved in immunotoxic effects of environmental contaminants. The aims of the present review are to critically discuss the available knowledge on (i) the expression and possible function of the AhR in the immune systems of teleost fishes; and (ii) the impact of AhR-activating xenobiotics on the immune systems of fish at the levels of immune gene expression, immune cell proliferation and immune cell function, immune pathology, and resistance to infectious disease. The existing information indicates that the AhR is expressed in the fish immune system, but currently, we have little understanding of its physiological role. Exposure to AhR-activating contaminants results in the modulation of numerous immune structural and functional parameters of fish. Despite the diversity of fish species studied and the experimental conditions investigated, the published findings rather uniformly point to immunosuppressive actions of xenobiotic AhR ligands in fish. These effects are often associated with increased disease susceptibility. The fact that fish populations from HAH- and PAH-contaminated environments suffer immune disturbances and elevated disease susceptibility highlights that the immunotoxic effects of AhR-activating xenobiotics bear environmental relevance.

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Section: The Ahr In Fishmentioning

confidence: 99%

Section: The Ahr In Fishmentioning

confidence: 99%

Immunotoxicity of Xenobiotics in Fish: A Role for the Aryl Hydrocarbon Receptor (AhR)?

Segner

Bailey²,

Tafalla³

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…AhR-deficient models exhibited several morphological defects, supporting the involvement of the protein in differentiation and development. The zebrafish ( Danio rerio ) is another well-established vertebrate model used to untangle the AhR pathway ( Shankar et al, 2020 ). In contrast to mammals, which express a single AhR gene, zebrafish exhibits three AhR genes ( ahr1a , ahr1b , and ahr2 ) due to a pair of whole-genome duplication (WGD) events in early vertebrate lineage followed by an additional teleost-specific WGD that happened about 350 mya ( Glasauer and Neuhauss, 2014 ).…”

Section: Novel Functions For An Old System: Advancements and Perspectivesmentioning

confidence: 99%

Where the Aryl Hydrocarbon Receptor Meets the microRNAs: Literature Review of the Last 10 Years

Disner

Lopes-Ferreira

Lima

2021

Front. Mol. Biosci.

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The aryl hydrocarbon receptor (AhR) is an environmentally responsive ligand-activated transcription factor, identified in the ‘70s for its toxic responses to halogenated polycyclic aromatic hydrocarbons, such as dioxin. Recently, AhR has been recognized as engaged in multiple physiological processes in health and diseases, particularly in the immune system, inflammatory response, tumorigenesis, and cellular differentiation by epigenetic mechanisms involving miRNAs. However, there is still scarce information about AhR-dependent miRNA regulation and miRNA-mediated epigenetic control in pathologies and therapies. In this review, we explore the mutual regulation of AhR and miRNA over the last decade of studies since many miRNAs have dioxin response elements (DRE) in their 3’ UTR, as well as AhR might contain binding sites of miRNAs. TCDD is the most used ligand to investigate the impact of AhR activation, and the immune system is one of the most sensitive of its targets. An association between TCDD-activated AhR and epigenetic mechanisms like post-transcriptional regulation by miRNAs, DNA methylation, or histone modification has already been confirmed. Besides, several studies have shown that AhR-induced miR-212/132 cluster suppresses cancers, attenuates autoimmune diseases, and has an anti-inflammatory role in different immune responses by regulating cytokine levels and immune cells. Together the ever-expanding new AhR roles and the miRNA therapeutics are a prominent segment among biopharmaceuticals. Additionally, AhR-activated miRNAs can serve as valuable biomarkers of diseases, notably cancer progression or suppression and chemical exposure. Once AhR-dependent gene expression may hinge on the ligand, cell type, and context singularity, the reviewed outcomes might help contextualize state of the art and support new trends and emerging opportunities in the field.

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“…This pollutant induces the enzyme CYP1A that helps degrade and clear xenobiotics but that also activates some substrates to electrophiles that damage cellular macromolecules. Sturgeon have two forms of aryl hydrocarbon receptor (AHR1, AHR2), where the latter is responsible for induction of CYP1A and most of the myriad deleterious effects of TCDD and similar ligands [ 9 , 10 ]. TCDD can act as an endocrine disruptor, for example, by suppressing estrogenic responsiveness (vitellogenin synthesis) in white sturgeon [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Epidermal cell cultures from white and green sturgeon (Acipenser transmontanus and medirostris): Expression of TGM1-like transglutaminases and CYP4501A

et al. 2022

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Using a system optimized for propagating human keratinocytes, culture of skin samples from white and green sturgeons generated epithelial cells capable of making cross-linked protein envelopes. Two distinct forms of TGM1-like mRNA were molecularly cloned from the cells of white sturgeon and detected in green sturgeon cells, accounting for their cellular envelope forming ability. The protein translated from each displayed a cluster of cysteine residues resembling the membrane anchorage region expressed in epidermal cells of teleosts and tetrapods. One of the two mRNA forms (called A) was present at considerably higher levels than the other (called B) in both species. Continuous lines of white sturgeon epidermal cells were established and characterized. Size measurements indicated that a substantial fraction of the cells became enlarged, appearing similar to squames in human epidermal keratinocyte cultures. The cultures also expressed CYP1A, a cytochrome P450 enzyme inducible by activation of aryl hydrocarbon receptor 2 in fish. The cells gradually improved in growth rate over a dozen passages while retaining envelope forming ability, TGM1 expression and CYP1A inducibility. These cell lines are thus potential models for studying evolution of fish epidermis leading to terrestrial adaptation and for testing sturgeon sensitivity to environmental stresses such as pollution.

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A Review of the Functional Roles of the Zebrafish Aryl Hydrocarbon Receptors

Cited by 33 publications

References 222 publications

Immunotoxicity of Xenobiotics in Fish: A Role for the Aryl Hydrocarbon Receptor (AhR)?

Immunotoxicity of Xenobiotics in Fish: A Role for the Aryl Hydrocarbon Receptor (AhR)?

Where the Aryl Hydrocarbon Receptor Meets the microRNAs: Literature Review of the Last 10 Years

Epidermal cell cultures from white and green sturgeon (Acipenser transmontanus and medirostris): Expression of TGM1-like transglutaminases and CYP4501A

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