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  1. Article ; Online: Environmentally realistic concentrations of chlorinated, brominated, and fluorinated persistent organic pollutants induce the unfolded protein response as a shared stress pathway in the liver of Atlantic cod (Gadus morhua).

    Olsvik, Pål A / Meier, Sonnich / Zhang, Xiaokang / Goksøyr, Anders / Karlsen, Odd Andre / Yadetie, Fekadu

    Journal of applied toxicology : JAT

    2023  Volume 43, Issue 12, Page(s) 1859–1871

    Abstract: In the North Sea and North Atlantic coastal areas, fish experience relatively high background levels of persistent organic pollutants. This study aimed to compare the mode of action of environmentally relevant concentrations of mixtures of halogenated ... ...

    Abstract In the North Sea and North Atlantic coastal areas, fish experience relatively high background levels of persistent organic pollutants. This study aimed to compare the mode of action of environmentally relevant concentrations of mixtures of halogenated compounds in Atlantic cod. Juvenile male cod with mean weight of 840 g were exposed by gavage to dietary mixtures of chlorinated (PCBs, DDT analogs, chlordane, lindane, and toxaphene), brominated (PBDEs), and fluorinated (PFOS) compounds for 4 weeks. One group received a combined mixture of all three compound groups. The results showed that the accumulated levels of chemicals in cod liver after 4 weeks of exposure reflected concentrations found in wild fish in this region. Pathway analysis revealed that the treatment effects by each of the three groups of chemicals (chlorinated, brominated, and fluorinated) converged on activation of the unfolded protein response (UPR). Upstream regulator analysis predicted that almost all the key transcription factors (XBP1, ERN1, ATF4, EIF2AK3, and NFE2L2) regulating the UPR were significantly activated. No additive effect was observed in cod co-treated with all three compound groups. In conclusion, the genome-wide transcriptomic study suggests that the UPR pathway is a sensitive common target of halogenated organic environmental pollutants in fish.
    MeSH term(s) Animals ; Male ; Gadus morhua/metabolism ; Persistent Organic Pollutants/metabolism ; Persistent Organic Pollutants/pharmacology ; Liver ; Polychlorinated Biphenyls/analysis ; Environmental Pollutants/analysis ; Water Pollutants, Chemical/analysis
    Chemical Substances Persistent Organic Pollutants ; Polychlorinated Biphenyls (DFC2HB4I0K) ; Environmental Pollutants ; Water Pollutants, Chemical
    Language English
    Publishing date 2023-08-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604625-3
    ISSN 1099-1263 ; 0260-437X
    ISSN (online) 1099-1263
    ISSN 0260-437X
    DOI 10.1002/jat.4519
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1661: Show issues Location:
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  2. Article ; Online: PCB-126 spiked to polyethylene microplastic ingested by juvenile Atlantic cod (Gadus morhua) accumulates in liver and muscle tissues

    Bogevik, André S. / Ytteborg, Elisabeth / Madsen, Alexander Klevedal / Jordal, Ann-Elise Olderbakk / Karlsen, Odd André / Rønnestad, Ivar

    Marine Pollution Bulletin. 2023 Feb., v. 187 p.114528-

    2023  

    Abstract: In the present study, polyethylene (PE) microplastics (150-300 μm) were added to Atlantic cod (Gadus morhua) feeds at 1 %, either in their present form (Virgin PE) or spiked with PCB-126 (Spiked PE). The feeds were given to juvenile cod for a 4-week ... ...

    Abstract In the present study, polyethylene (PE) microplastics (150-300 μm) were added to Atlantic cod (Gadus morhua) feeds at 1 %, either in their present form (Virgin PE) or spiked with PCB-126 (Spiked PE). The feeds were given to juvenile cod for a 4-week period. The fish grew from 11 to 23 g with no significant difference between dietary treatments. Cod fed spiked PE showed a significantly higher concentration of PCB-126 in liver and muscle samples compared to control and fish ingesting virgin PE. In accordance with the accumulation of PCB-126 in the liver, the expression of hepatic cyp1a was higher in cod fed spiked PE. Notably, we observed that spiked PE, as well as virgin PE, have an effect on skin. Overall changes indicated a reduced skin barrier in fish fed a diet containing PE. Indicating that PE itself through interaction with gut tissue may influence skin health in fish.
    Keywords Gadus morhua ; diet ; fish ; juveniles ; liver ; marine pollution ; microplastics ; muscles ; polyethylene ; Atlantic cod ; Gene expression ; PCB ; Toxicology
    Language English
    Dates of publication 2023-02
    Publishing place Elsevier Ltd
    Document type Article ; Online
    Note Use and reproduction
    ZDB-ID 2001296-2
    ISSN 1879-3363 ; 0025-326X
    ISSN (online) 1879-3363
    ISSN 0025-326X
    DOI 10.1016/j.marpolbul.2022.114528
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  3. Article ; Online: PCB-126 spiked to polyethylene microplastic ingested by juvenile Atlantic cod (Gadus morhua) accumulates in liver and muscle tissues.

    Bogevik, André S / Ytteborg, Elisabeth / Madsen, Alexander Klevedal / Jordal, Ann-Elise Olderbakk / Karlsen, Odd André / Rønnestad, Ivar

    Marine pollution bulletin

    2023  Volume 187, Page(s) 114528

    Abstract: In the present study, polyethylene (PE) microplastics (150-300 μm) were added to Atlantic cod (Gadus morhua) feeds at 1 %, either in their present form (Virgin PE) or spiked with PCB-126 (Spiked PE). The feeds were given to juvenile cod for a 4-week ... ...

    Abstract In the present study, polyethylene (PE) microplastics (150-300 μm) were added to Atlantic cod (Gadus morhua) feeds at 1 %, either in their present form (Virgin PE) or spiked with PCB-126 (Spiked PE). The feeds were given to juvenile cod for a 4-week period. The fish grew from 11 to 23 g with no significant difference between dietary treatments. Cod fed spiked PE showed a significantly higher concentration of PCB-126 in liver and muscle samples compared to control and fish ingesting virgin PE. In accordance with the accumulation of PCB-126 in the liver, the expression of hepatic cyp1a was higher in cod fed spiked PE. Notably, we observed that spiked PE, as well as virgin PE, have an effect on skin. Overall changes indicated a reduced skin barrier in fish fed a diet containing PE. Indicating that PE itself through interaction with gut tissue may influence skin health in fish.
    MeSH term(s) Animals ; Gadus morhua ; Plastics/metabolism ; Microplastics ; Polyethylene/metabolism ; Liver/metabolism ; Fishes/metabolism ; Muscles
    Chemical Substances 3,4,5,3',4'-pentachlorobiphenyl (TSH69IA9XF) ; Plastics ; Microplastics ; Polyethylene (9002-88-4)
    Language English
    Publishing date 2023-01-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 2001296-2
    ISSN 1879-3363 ; 0025-326X
    ISSN (online) 1879-3363
    ISSN 0025-326X
    DOI 10.1016/j.marpolbul.2022.114528
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  4. Article: Single PFAS and PFAS mixtures affect nuclear receptor- and oxidative stress-related pathways in precision-cut liver slices of Atlantic cod (Gadus morhua)

    Dale, Karina / Yadetie, Fekadu / Horvli, Torill / Zhang, Xiaokang / Frøysa, Håvard Guldbrandsen / Karlsen, Odd André / Goksøyr, Anders

    Science of the total environment. 2022 Mar. 25, v. 814

    2022  

    Abstract: The aim of the present study was to investigate effects of per- and polyfluoroalkyl substances (PFAS), both single compounds and a mixture of these, using precision-cut liver slices (PCLS) from Atlantic cod (Gadus morhua). PCLS were exposed for 48 h to ... ...

    Abstract The aim of the present study was to investigate effects of per- and polyfluoroalkyl substances (PFAS), both single compounds and a mixture of these, using precision-cut liver slices (PCLS) from Atlantic cod (Gadus morhua). PCLS were exposed for 48 h to perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) (10, 50 and 100 μM), and three mixtures of these at equimolar concentrations (10, 50 and 100 μM). Transcriptomic responses were assessed using RNA sequencing. Among exposures to single PFAS, PFOS produced the highest number of differentially expressed genes (DEGs) compared to PFOA and PFNA (86, 25 and 31 DEGs, respectively). Exposure to the PFAS mixtures resulted in a markedly higher number of DEGs (841). Clustering analysis revealed that the expression pattern of the PFAS mixtures were more similar to PFOS compared to PFOA and PFNA, suggesting that effects induced by the PFAS mixtures may largely be attributed to PFOS. Pathway analysis showed significant enrichment of pathways related to oxidative stress, cholesterol metabolism and nuclear receptors in PFOS-exposed PCLS. Fewer pathways were significantly enriched following PFOA and PFNA exposure alone. Significantly enriched pathways following mixture exposure included lipid biosynthesis, cancer-related pathways, nuclear receptor pathways and oxidative stress-related pathways such as ferroptosis. The expression of most of the genes within these pathways was increased following PFAS exposure. Analysis of non-additive effects in the 100 μM PFAS mixture highlighted genes involved in the antioxidant response and membrane transport, among others, and the majority of these genes had synergistic expression patterns in the mixture. Nevertheless, 90% of the DEGs following mixture exposure showed additive expression patterns, suggesting additivity to be the major mixture effect. In summary, PFAS exposure promoted effects on cellular processes involved in oxidative stress, nuclear receptor pathways and sterol metabolism in cod PCLS, with the strongest effects observed following PFAS mixture exposure.
    Keywords Gadus morhua ; RNA ; antioxidant activity ; biosynthesis ; cholesterol metabolism ; environment ; ferroptosis ; gene expression regulation ; liver ; oxidative stress ; perfluorooctane sulfonic acid ; perfluorooctanoic acid ; sterols ; transcriptomics
    Language English
    Dates of publication 2022-0325
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 121506-1
    ISSN 1879-1026 ; 0048-9697
    ISSN (online) 1879-1026
    ISSN 0048-9697
    DOI 10.1016/j.scitotenv.2021.152732
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    In stock of ZB MED Bonn / Germany

    Z 74/341: Show issues

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  5. Article: Transcriptome responses in copepods Calanus finmarchicus, Calanus glacialis and Calanus hyperboreus exposed to phenanthrene and benzo[a]pyrene

    Yadetie, Fekadu / Brun, Nadja R. / Giebichenstein, Julia / Dmoch, Katarzyna / Hylland, Ketil / Borgå, Katrine / Karlsen, Odd André / Goksøyr, Anders

    Marine genomics. 2022 Oct., v. 65

    2022  

    Abstract: Arctic and sub-arctic pelagic organisms can be exposed to effluents and spills from offshore petroleum-related activities and thus it is important to understand how they respond to crude oil related contaminants such as polycyclic aromatic hydrocarbons ( ... ...

    Abstract Arctic and sub-arctic pelagic organisms can be exposed to effluents and spills from offshore petroleum-related activities and thus it is important to understand how they respond to crude oil related contaminants such as polycyclic aromatic hydrocarbons (PAHs). The copepod species Calanus finmarchicus, Calanus glacialis and Calanus hyperboreus represent key links in the arctic marine food web. We performed a transcriptome analysis of the three species exposed to phenanthrene (Phe) and benzo[a]pyrene (BaP) representing low and high molecular weight PAHs, respectively. Differential expression of several genes involved in many cellular pathways was observed after 72 h exposure to Phe (0.1 μM) and BaP (0.1 μM). In C. finmarchicus and C. glacialis, the exposure resulted in up-regulation of genes encoding enzymes in xenobiotic biotransformation, particularly the phase II cytosolic sulfonation system that include 3′-phosphoadenosine 5′-phosphosulfate synthase (PAPSS) and sulfotransferases (SULTs). The sulfonation pathway genes were more strongly induced by BaP than Phe in C. finmarchicus and C. glacialis but were not affected in C. hyperboreus. However, a larger number of genes and pathways were modulated in C. hyperboreus by the PAHs including genes encoding xenobiotic biotransformation and lipid metabolism enzymes, suggesting stronger responses in this species. The results suggest that the cytosolic sulfonation is a major phase II conjugation pathway for PAHs in C. finmarchicus and C. glacialis. Some of the biotransformation systems affected are known to be involved in metabolism of endogenous compounds such as ecdysteroids, which may suggest potential interference with physiological and developmental processes of the copepod species.
    Keywords Calanus finmarchicus ; aquatic food webs ; biotransformation ; ecdysteroids ; gene expression regulation ; genomics ; lipid metabolism ; molecular weight ; petroleum ; phenanthrenes ; sulfotransferases ; transcriptome ; transcriptomics ; xenobiotics ; Arctic region
    Language English
    Dates of publication 2022-10
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 2429626-0
    ISSN 1876-7478 ; 1874-7787
    ISSN (online) 1876-7478
    ISSN 1874-7787
    DOI 10.1016/j.margen.2022.100981
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  6. Article ; Online: Toxicity assessment of urban marine sediments from Western Norway using a battery of stress-activated receptors and cell-based bioassays from fish.

    Goksøyr, Siri Øfsthus / Sørensen, Helene / Grøsvik, Bjørn Einar / Pampanin, Daniela M / Goksøyr, Anders / Karlsen, Odd André

    Environmental toxicology and pharmacology

    2021  Volume 87, Page(s) 103704

    Abstract: A luciferase reporter gene-based bioassay battery consisting of stress-activated receptors from fish, complemented with traditional fish cell-based bioassays, were used to assess the toxicity of marine sediment samples from the Byfjorden area around the ... ...

    Abstract A luciferase reporter gene-based bioassay battery consisting of stress-activated receptors from fish, complemented with traditional fish cell-based bioassays, were used to assess the toxicity of marine sediment samples from the Byfjorden area around the city of Bergen (Norway). The reporter assays covered a wide range of cellular signalling and metabolic pathways, representing different molecular initiating events in the adverse outcome pathway framework. Cytotoxicity, generation of reactive oxygen-species, and induction of 7-ethoxyresorufin-O-deethylase activity were analysed using fish liver and gill cell lines. Chemical analyses of the sediment extracts revealed complex contamination profiles, especially at the innermost stations, which contained a wide array of persistent organic pollutants, polycyclic aromatic hydrocarbons, and metals. Sediment extracts from these sites were more potent in activating the stress-activated receptors than the other extracts, reflecting their toxicant profiles. Importantly, receptor- and cell-based bioassays complemented the chemical analyses and provided important data for future environmental risk assessments of urban marine sediments.
    MeSH term(s) Animals ; Biological Assay ; Cell Line ; Cell Survival/drug effects ; Cytochrome P-450 CYP1A1/metabolism ; Fishes ; Genes, Reporter ; Geologic Sediments ; Halogenated Diphenyl Ethers/analysis ; Halogenated Diphenyl Ethers/toxicity ; Hydrocarbons, Chlorinated/analysis ; Hydrocarbons, Chlorinated/toxicity ; Luciferases/genetics ; Metals, Heavy/analysis ; Metals, Heavy/toxicity ; Norway ; Polycyclic Aromatic Hydrocarbons/analysis ; Polycyclic Aromatic Hydrocarbons/toxicity ; Reactive Oxygen Species/metabolism ; Water Pollutants, Chemical/analysis ; Water Pollutants, Chemical/toxicity
    Chemical Substances Halogenated Diphenyl Ethers ; Hydrocarbons, Chlorinated ; Metals, Heavy ; Polycyclic Aromatic Hydrocarbons ; Reactive Oxygen Species ; Water Pollutants, Chemical ; Luciferases (EC 1.13.12.-) ; Cytochrome P-450 CYP1A1 (EC 1.14.14.1)
    Language English
    Publishing date 2021-07-14
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1318302-3
    ISSN 1872-7077 ; 1382-6689
    ISSN (online) 1872-7077
    ISSN 1382-6689
    DOI 10.1016/j.etap.2021.103704
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4490: Show issues Location:
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  7. Article ; Online: Transcriptome responses in polar cod (Boreogadus saida) liver slice culture exposed to benzo[a]pyrene and ethynylestradiol: insights into anti-estrogenic effects.

    Yadetie, Fekadu / Brun, Nadja R / Vieweg, Ireen / Nahrgang, Jasmine / Karlsen, Odd André / Goksøyr, Anders

    Toxicology in vitro : an international journal published in association with BIBRA

    2021  Volume 75, Page(s) 105193

    Abstract: Polar cod (Boreogadus saida) is a key species in the arctic marine ecosystem vulnerable to effects of pollution, particularly from petroleum related activities. To facilitate studying the effects of those pollutants, we adapted a precision-cut liver ... ...

    Abstract Polar cod (Boreogadus saida) is a key species in the arctic marine ecosystem vulnerable to effects of pollution, particularly from petroleum related activities. To facilitate studying the effects of those pollutants, we adapted a precision-cut liver slice culture protocol for this species. Using this system on board a research vessel, we studied gene expression in liver slice after exposure to the polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BaP), ethynylestradiol (EE2), and their mixtures, to map their molecular targets and examine possible anti-estrogenic effects of BaP. The exposure experiments were performed with BaP alone (0.1, 1, and 10 μM) or in combination with low concentrations of EE2 (5 nM) to mimic physiological estradiol levels in early vitellogenic female fish. Transcriptome analysis (RNA-seq) was performed after 72 h exposure in culture to map the genes and cellular pathways affected. The results provide a view of global transcriptome responses to BaP and EE2, which resulted in enrichment of many pathways such as the aryl hydrocarbon (Ahr) and estrogen receptor pathways. In the mixture exposure, BaP resulted in anti-estrogenic effects, shown by attenuation of EE2 activated transcription of many estrogen target genes. The results from this ex vivo experiment suggest that pollutants that activate the Ahr pathway such as the PAH compound BaP can result in anti-estrogenic effects that may lead to endocrine disruption in polar cod.
    MeSH term(s) Animals ; Benzo(a)pyrene/pharmacology ; Estrogen Antagonists/pharmacology ; Estrogens/pharmacology ; Ethinyl Estradiol/pharmacology ; Female ; Gadiformes/genetics ; Gene Expression Profiling ; Liver/drug effects ; Liver/metabolism ; Tissue Culture Techniques ; Transcriptome/drug effects ; Vitellogenins/metabolism
    Chemical Substances Estrogen Antagonists ; Estrogens ; Vitellogenins ; Benzo(a)pyrene (3417WMA06D) ; Ethinyl Estradiol (423D2T571U)
    Language English
    Publishing date 2021-05-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 639064-x
    ISSN 1879-3177 ; 0887-2333
    ISSN (online) 1879-3177
    ISSN 0887-2333
    DOI 10.1016/j.tiv.2021.105193
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2223: Show issues Location:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
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  8. Article: Substituted Two- to Five-Ring Polycyclic Aromatic Compounds Are Potent Agonists of Atlantic Cod (Gadus morhua) Aryl Hydrocarbon Receptors Ahr1a and Ahr2a

    Lille-Langøy, Roger / Jørgensen, Kåre Bredeli / Goksøyr, Anders / Pampanin, Daniela M. / Sydnes, Magne O. / Karlsen, Odd André

    Environmental science & technology. 2021 Nov. 05, v. 55, no. 22

    2021  

    Abstract: Polycyclic aromatic hydrocarbons (PAHs) are among the most toxic and bioavailable components found in petroleum and represent a high risk to aquatic organisms. The aryl hydrocarbon receptor (Ahr) is a ligand-activated transcription factor that mediates ... ...

    Abstract Polycyclic aromatic hydrocarbons (PAHs) are among the most toxic and bioavailable components found in petroleum and represent a high risk to aquatic organisms. The aryl hydrocarbon receptor (Ahr) is a ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other planar aromatic hydrocarbons, including certain PAHs. Ahr acts as a xenosensor and modulates the transcription of biotransformation genes in vertebrates, such as cytochrome P450 1A (cyp1a). Atlantic cod (Gadus morhua) possesses two Ahr proteins, Ahr1a and Ahr2a, which diverge in their primary structure, tissue-specific expression, ligand affinities, and transactivation profiles. Here, a luciferase reporter gene assay was used to assess the sensitivity of the Atlantic cod Ahrs to 31 polycyclic aromatic compounds (PACs), including two- to five-ring native PAHs, a sulfur-containing heterocyclic PAC, as well as several methylated, methoxylated, and hydroxylated congeners. Notably, most parent compounds, including naphthalene, phenanthrene, and partly, chrysene, did not act as agonists for the Ahrs, while hydroxylated and/or alkylated versions of these PAHs were potent agonists. Importantly, the greater potencies of substituted PAH derivatives and their ubiquitous occurrence in nature emphasize that more knowledge on the toxicity of these environmentally and toxicologically relevant compounds is imperative.
    Keywords Gadus morhua ; aryl hydrocarbon receptors ; bioavailability ; biotransformation ; cytochrome P-450 ; environmental science ; hydroxylation ; ligands ; luciferase ; methylation ; naphthalene ; petroleum ; phenanthrenes ; reporter genes ; risk ; technology ; tetrachlorodibenzo-p-dioxin ; toxicity ; transcriptional activation
    Language English
    Dates of publication 2021-1105
    Size p. 15123-15135.
    Publishing place American Chemical Society
    Document type Article
    ISSN 1520-5851
    DOI 10.1021/acs.est.1c02946
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  9. Article ; Online: Transcriptome responses in copepods Calanus finmarchicus, Calanus glacialis and Calanus hyperboreus exposed to phenanthrene and benzo[a]pyrene.

    Yadetie, Fekadu / Brun, Nadja R / Giebichenstein, Julia / Dmoch, Katarzyna / Hylland, Ketil / Borgå, Katrine / Karlsen, Odd André / Goksøyr, Anders

    Marine genomics

    2022  Volume 65, Page(s) 100981

    Abstract: Arctic and sub-arctic pelagic organisms can be exposed to effluents and spills from offshore petroleum-related activities and thus it is important to understand how they respond to crude oil related contaminants such as polycyclic aromatic hydrocarbons ( ... ...

    Abstract Arctic and sub-arctic pelagic organisms can be exposed to effluents and spills from offshore petroleum-related activities and thus it is important to understand how they respond to crude oil related contaminants such as polycyclic aromatic hydrocarbons (PAHs). The copepod species Calanus finmarchicus, Calanus glacialis and Calanus hyperboreus represent key links in the arctic marine food web. We performed a transcriptome analysis of the three species exposed to phenanthrene (Phe) and benzo[a]pyrene (BaP) representing low and high molecular weight PAHs, respectively. Differential expression of several genes involved in many cellular pathways was observed after 72 h exposure to Phe (0.1 μM) and BaP (0.1 μM). In C. finmarchicus and C. glacialis, the exposure resulted in up-regulation of genes encoding enzymes in xenobiotic biotransformation, particularly the phase II cytosolic sulfonation system that include 3'-phosphoadenosine 5'-phosphosulfate synthase (PAPSS) and sulfotransferases (SULTs). The sulfonation pathway genes were more strongly induced by BaP than Phe in C. finmarchicus and C. glacialis but were not affected in C. hyperboreus. However, a larger number of genes and pathways were modulated in C. hyperboreus by the PAHs including genes encoding xenobiotic biotransformation and lipid metabolism enzymes, suggesting stronger responses in this species. The results suggest that the cytosolic sulfonation is a major phase II conjugation pathway for PAHs in C. finmarchicus and C. glacialis. Some of the biotransformation systems affected are known to be involved in metabolism of endogenous compounds such as ecdysteroids, which may suggest potential interference with physiological and developmental processes of the copepod species.
    MeSH term(s) Animals ; Benzo(a)pyrene/metabolism ; Benzo(a)pyrene/toxicity ; Copepoda/genetics ; Copepoda/metabolism ; Phenanthrenes/metabolism ; Phenanthrenes/toxicity ; Polycyclic Aromatic Hydrocarbons ; Transcriptome ; Water Pollutants, Chemical/toxicity ; Xenobiotics
    Chemical Substances Phenanthrenes ; Polycyclic Aromatic Hydrocarbons ; Water Pollutants, Chemical ; Xenobiotics ; Benzo(a)pyrene (3417WMA06D)
    Language English
    Publishing date 2022-08-12
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2429626-0
    ISSN 1876-7478 ; 1874-7787
    ISSN (online) 1876-7478
    ISSN 1874-7787
    DOI 10.1016/j.margen.2022.100981
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  10. Article ; Online: Agonistic and potentiating effects of perfluoroalkyl substances (PFAS) on the Atlantic cod (Gadus morhua) peroxisome proliferator-activated receptors (Ppars).

    Søderstrøm, Sofie / Lille-Langøy, Roger / Yadetie, Fekadu / Rauch, Mateusz / Milinski, Ana / Dejaegere, Annick / Stote, Roland H / Goksøyr, Anders / Karlsen, Odd André

    Environment international

    2022  Volume 163, Page(s) 107203

    Abstract: Toxicity mediated by per- and polyfluoroalkyl substances (PFAS), and especially perfluoroalkyl acids (PFAAs), has been linked to activation of peroxisome proliferator-activated receptors (Ppar) in many vertebrates. Here, we present the primary structures, ...

    Abstract Toxicity mediated by per- and polyfluoroalkyl substances (PFAS), and especially perfluoroalkyl acids (PFAAs), has been linked to activation of peroxisome proliferator-activated receptors (Ppar) in many vertebrates. Here, we present the primary structures, phylogeny, and tissue-specific distributions of the Atlantic cod (Gadus morhua) gmPpara1, gmPpara2, gmPparb, and gmPparg, and demonstrate that the carboxylic acids PFHxA, PFOA, PFNA, as well as the sulfonic acid PFHxS, activate gmPpara1 in vitro, which was also supported by in silico analyses. Intriguingly, a binary mixture of PFOA and the non-activating PFOS produced a higher activation of gmPpara1 compared to PFOA alone, suggesting that PFOS has a potentiating effect on receptor activation. Supporting the experimental data, docking and molecular dynamics simulations of single and double-ligand complexes led to the identification of a putative allosteric binding site, which upon binding of PFOS stabilizes an active conformation of gmPpara1. Notably, binary exposures of gmPpara1, gmPpara2, and gmPparb to model-agonists and PFAAs produced similar potentiating effects. This study provides novel mechanistic insights into how PFAAs may modulate the Ppar signaling pathway by either binding the canonical ligand-binding pocket or by interacting with an allosteric binding site. Thus, individual PFAAs, or mixtures, could potentially modulate the Ppar-signaling pathway in Atlantic cod by interfering with at least one gmPpar subtype.
    MeSH term(s) Alkanesulfonic Acids/toxicity ; Animals ; Environmental Pollutants ; Fluorocarbons/analysis ; Gadus morhua ; Gonadal Steroid Hormones ; Ligands ; Peroxisome Proliferator-Activated Receptors
    Chemical Substances Alkanesulfonic Acids ; Environmental Pollutants ; Fluorocarbons ; Gonadal Steroid Hormones ; Ligands ; Peroxisome Proliferator-Activated Receptors
    Language English
    Publishing date 2022-03-29
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 554791-x
    ISSN 1873-6750 ; 0160-4120
    ISSN (online) 1873-6750
    ISSN 0160-4120
    DOI 10.1016/j.envint.2022.107203
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