Cytochrome P450 1 enzymes in black rockfish, Sebastes schlegelii: Molecular characterization and expression patterns after exposure to benzo[a]pyrene

Woo, Soo Ji; Chung, Joon Ki

doi:10.1016/j.aquatox.2020.105566

Cited by 14 publications

(4 citation statements)

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“…This study found an important role of nuclear receptors PXR and CAR in regulation of CYP450 and UGT1A1 in hypoxia. Other studies shown that hypoxia significantly increased the expression of AhR (Aryl hydrocarbon receptor) who is the main transcription factor affecting CYP450 1 enzymes (Soo and Joon, 2020;Nuno et al, 2020). Whether AhR affects CYP450 and UGT1A1 under hypoxia environment needs further evaluation.…”

Section: Discussionmentioning

confidence: 97%

Regulation of High-Altitude Hypoxia on the Transcription of CYP450 and UGT1A1 Mediated by PXR and CAR

et al. 2020

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Little is known about what roles the pregnane X receptor (PXR) and constitutive androstane receptor (CAR) play in drug metabolism in high-altitude hypoxia. Likewise, the potential interaction of nuclear receptors and drug metabolism enzymes during drug metabolism of high-altitude hypoxia is not fully understood. In this work, we investigated the effects of high-altitude hypoxia on transcriptional regulation of cytochrome P450 (CYP450) and UDP-glucuronosyltransferase 1A1 (UGT1A1) genes mediated by PXR and CAR proteins. The protein and mRNA expressions of CYP450, UGT1A1, PXR, and CAR were determined by enzyme-linked immunosorbent assay and qPCR in rats and HepG2 cell lines under hypoxia. Hypoxia potently inhibited the CYP450 isoforms, UGT1A1, PXR, and CAR protein and mRNA expression. To clarify whether PXR and CAR regulate various genes involved in drug metabolism of high-altitude hypoxia, we investigated the expression of CYP1A2, CYP2C9, CYP2E1, CYP3A4, and UGT1A1 using a dualluciferase reporter assay after treatment with Ketoconazole (KCZ) and Retinoic acid (RA), or silenced PXR and CAR gene expression. In HepG2 cells, hypoxia, KCZ, and RA inhibited CYP450 isoforms and UGT1A1 expression. Activation of PXR and CAR in cells treated with 6-(4-chlorophenyl)-imidazo (2,1-b) thiazole-5-carbaldehyde (CITCO) and rifampicin (Rif) resulted in the enhancement of CYP450 isoforms, UGT1A1, PXR, and CAR. In contrast, this effect was not observed under hypoxia. Taken together, our results suggest that hypoxia inhibits CYP1A2, CYP2C9, CYP2E1, CYP3A4, and UGT1A1 expression via the PXR and CAR regulatory pathway.

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Section: Discussionmentioning

confidence: 97%

Regulation of High-Altitude Hypoxia on the Transcription of CYP450 and UGT1A1 Mediated by PXR and CAR

et al. 2020

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“…This is presumed to be due to differences in susceptible species or exposure dose, and it needs to be further studied. Zebrafish and S. schlegelii have two CYP1Cs [58,59]. TCDD and β-NF induced the mRNA expression of two CYP1Cs in the mesencephalic vein of zebrafish, and the knockdown of each CYP1C prevented TCDD-induced mesencephalic vein circulation impairment [60].…”

Section: Discussionmentioning

confidence: 99%

Histopathological and Immunohistochemical Features and Expression Patterns of Cytochrome p450 1 Family Genes in Black Rockfish (Sebastes schlegelii): Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin and β-Naphthoflavone

Woo,

Joo,

Kim

et al. 2023

Fishes

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The climate crisis and growing petroleum demand have put the health of aquatic animals in jeopardy. Fish are sensitive to chemical pollutants in aquatic environments, such as polycyclic aromatic hydrocarbons, dioxins, and dibenzofurans. This study investigated the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and β-naphthoflavone (β-NF) exposure on histopathological and immunohistochemical features and expression patterns of cytochrome P450 1 (CYP1) family genes in black rockfish, Sebastes schlegelii. Histopathological alterations in the liver included congested central vein, sinusoidal dilatation, lymphocyte infiltration, and severe vacuolation within hepatocytes. The most prevalent alterations in TCDD-exposed kidneys were glomerular enlargement, narrowing of tubular lumen, melanomacrophage centers (MMCs), and necrosis. Moreover, CYP1A immunostaining was strong in renal tubules following TCDD exposure. All CYP1 family genes (CYP1A, CYP1B, CYP1C1, and CYP1C2) were significantly increased in the gills, liver, and kidney exposed to TCDD. Similarly, a significant increase of CYP1A mRNA expression in the kidney was observed upon exposure to TCDD (30.9-folds) and β-NF (25.5-folds) compared with that of the control group (p < 0.05). TCDD and β-NF exposure exerted more adverse effects on the kidney than the liver, and TCDD had a greater in vivo toxic effect than β-NF. The combined histopathological, immunohistochemical, and molecular alternations may be helpful for diagnosing chemical contaminant exposure in S. schlegelii.

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“…The CYP1A subfamily (Figure 7) is the most studied among the cytochrome P450 family of enzymes as it is significantly induced by PAHs. The activity of this marker in fish and shellfish has been applied in many assessments to verify PAH effects, especially BaP, which significantly increases the expression of CYP1A as a function of exposure time and dose [47,59,[85][86][87][88][89]92,93,100].…”

Section: Biomarker Evaluationsmentioning

confidence: 99%

The Role of the Ecotoxicology Applied to Seafood as a Tool for Human Health Risk Assessments Concerning Polycyclic Aromatic Hydrocarbons

Pinho

Rodrigues

Guimarães

et al. 2022

IJERPH

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Background: Polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants routinely detected in aquatic ecosystems. It is, therefore, necessary to assess the link between deleterious marine biota PAH effects, especially in commercialized and consumed animals, environmental health status, and potential human health risks originating from the consumption of contaminated seafood products. Thus, this review seeks to verify the relationships of ecotoxicological studies in determining effect and safety concentrations on animals routinely consumed by humans. Methods: A total of 52 published studies between 2011 and 2021, indexed in three databases, were selected following the PICO methodology, and information on test animals, evaluated PAH, and endpoints were extracted. Results: Benzo(a)pyrene and phenanthrene were the most investigated PAHs in terms of biomarkers and test organisms, and mussels were the most evaluated bioindicator species, with an emphasis on reproductive responses. Furthermore, despite the apparent correlation between environmental PAH dynamics and effects on aquatic biota and human health, few assessments have been performed in a multidisciplinary manner to evaluate these three variables together. Conclusions: The links between human and environmental sciences must be strengthened to enable complete and realistic toxicity assessments as despite the application of seafood assessments, especially to mussels, in bioassays, the connection between toxicological animal responses and risks associated with their consumption is still understudied.

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Cytochrome P450 1 enzymes in black rockfish, Sebastes schlegelii: Molecular characterization and expression patterns after exposure to benzo[a]pyrene

Cited by 14 publications

References 58 publications

Regulation of High-Altitude Hypoxia on the Transcription of CYP450 and UGT1A1 Mediated by PXR and CAR

Regulation of High-Altitude Hypoxia on the Transcription of CYP450 and UGT1A1 Mediated by PXR and CAR

Histopathological and Immunohistochemical Features and Expression Patterns of Cytochrome p450 1 Family Genes in Black Rockfish (Sebastes schlegelii): Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin and β-Naphthoflavone

The Role of the Ecotoxicology Applied to Seafood as a Tool for Human Health Risk Assessments Concerning Polycyclic Aromatic Hydrocarbons

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