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Hisato Iwata - One of the best experts on this subject based on the ideXlab platform.
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In vitro assessment of effects of persistent organic pollutants on the transactivation of estrogen receptor α and β (ERα and ERβ) from the Baikal Seal (Pusa sibirica)
Ecotoxicology and environmental safety, 2019Co-Authors: Yuka Yoshinouchi, Eun-young Kim, Masashi Hirano, Sachiko Shimizu, Jin-seon Lee, Ken-ichi Suzuki, Hisato IwataAbstract:Abstract To assess the effect of exposure to persistent organic pollutants (POPs) on the estrogen receptor (ER) signaling pathway in Baikal Seals (Pusa sibirica), we investigated the molecular characterizations and functions of two Baikal Seal ER (bsER) isoforms, bsERα and bsERβ. The bsERα and bsERβ cDNA clones isolated have an open reading frame of 595 and 530 amino acid residues, respectively. The tissue distribution analyses of bsER mRNAs showed that bsERα transcripts were primarily found in the ovary and uterus, and bsERβ in the muscle in wild Baikal Seals. The immunofluorescence staining assay showed that 17β-estradiol (E2) treatment promoted the nuclear translocation of in vitro-expressed bsERα. Transient transfection of bsERα in U2OS cells enhanced the transcription of pS2, an ER target gene of E2. We then measured bsER-mediated transactivation potencies of POPs in an in vitro reporter gene assay system, in which a bsERα or bsERβ expression vector was transfected into COS-1 cells. For comparison, transactivation potencies of POPs on mouse ERs (mERα and mERβ) were also evaluated in the same manner. Results showed significant dose-dependent responses of bsERs and mERs when treated with p,p’-dichlorodiphenyltrichloroethane (p,p’-DDT), and p,p’-dichlorodiphenyldichloroethylene (p,p’-DDE). bsERs and mERs showed no response when exposed to polychlorinated biphenyls (PCBs) or 2,3,7,8-tetrachlorodibenzo-p-dioxin. Comparison of the dose-response curves of DDTs across species (bsERs vs. mERs) showed that bsERα had a response similar to mERα, but bsERβ was less sensitive than mERβ. Comparing the lowest observable effective concentrations of p,p′-DDT (2.8 μM) and p,p′-DDE (10 μM) for in vitro bsERα-mediated transactivation with their hepatic concentrations in wild Baikal Seals indicated that some individuals accumulated these compounds at levels comparable to the effective concentrations, suggesting the potential disruption of the bsERα signaling pathway in the wild population by these compounds. Co-transfection experiments with bsER and the aryl hydrocarbon receptor (AHR) suggested that high accumulation of estrogenic compounds exerts a synergistic effect with dioxin-like congeners on ER signaling through AHR activation in the wild Seal population.
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In Vitro and In Silico Evaluations of Binding Affinities of Perfluoroalkyl Substances to Baikal Seal and Human Peroxisome Proliferator-Activated Receptor α
Environmental science & technology, 2019Co-Authors: Hiroshi Ishibashi, Eun-young Kim, Masashi Hirano, Hisato IwataAbstract:In this study, we assessed the binding affinities of perfluoroalkyl substances (PFASs), including perfluoroalkyl carboxylates (PFCAs) and perfluoroalkyl sulfonates (PFSAs), to the ligand-binding domains (LBDs) of Baikal Seal (Pusa sibirica; bs) and human (h) peroxisome proliferator-activated receptor alpha (PPARα). An in vitro competitive binding assay showed that six PFCAs and two PFSAs could bind to recombinant bs and hPPARα LBD proteins in a dose-dependent manner. The relative binding affinities (RBAs) of PFASs to bsPPARα were as follows: PFOS > PFDA > PFNA > PFUnDA > PFOA > PFHxS > PFHpA > PFHxA. The RBAs to bsPPARα showed a significant positive correlation with those to hPPARα. In silico PPARα homology modeling predicted that there were two ligand-binding pockets (LBPs) in the bsPPARα and hPPARα LBDs. Structure–activity relationship analyses suggested that the binding potencies of PFASs to PPARα might depend on LBP binding cavity volume, hydrogen bond interactions, the number of perfluorinated carbon...
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In Vitro and In Silico Evaluations of Binding Affinities of Perfluoroalkyl Substances to Baikal Seal and Human Peroxisome Proliferator-Activated Receptor α
2019Co-Authors: Hiroshi Ishibashi, Eun-young Kim, Masashi Hirano, Hisato IwataAbstract:In this study, we assessed the binding affinities of perfluoroalkyl substances (PFASs), including perfluoroalkyl carboxylates (PFCAs) and perfluoroalkyl sulfonates (PFSAs), to the ligand-binding domains (LBDs) of Baikal Seal (Pusa sibirica; bs) and human (h) peroxisome proliferator-activated receptor alpha (PPARα). An in vitro competitive binding assay showed that six PFCAs and two PFSAs could bind to recombinant bs and hPPARα LBD proteins in a dose-dependent manner. The relative binding affinities (RBAs) of PFASs to bsPPARα were as follows: PFOS > PFDA > PFNA > PFUnDA > PFOA > PFHxS > PFHpA > PFHxA. The RBAs to bsPPARα showed a significant positive correlation with those to hPPARα. In silico PPARα homology modeling predicted that there were two ligand-binding pockets (LBPs) in the bsPPARα and hPPARα LBDs. Structure–activity relationship analyses suggested that the binding potencies of PFASs to PPARα might depend on LBP binding cavity volume, hydrogen bond interactions, the number of perfluorinated carbons, and the hydrophobicity of PFASs. Interspecies comparison of the in vitro binding affinities revealed that bsPPARα had higher preference for PFASs with long carbon chains than hPPARα. The in silico docking simulations suggested that the first LBP of bsPPARα had higher affinities than that of hPPARα; however, the second LBP of bsPPARα had lower affinities than that of hPPARα. To our knowledge, this is the first evidence showing interspecies differences in the binding of PFASs to PPARαs and their structure–activity relationships
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In Vitro Assessment of Activation of Baikal Seal ( Pusa sibirica) Peroxisome Proliferator-Activated Receptor α by Polybrominated Diphenyl Ethers.
Environmental science & technology, 2018Co-Authors: Hiroshi Ishibashi, Eun-young Kim, Koji Arizono, Hisato IwataAbstract:We investigated the Baikal Seal ( Pusa sibirica) peroxisome proliferator-activated receptor α (bsPPARα) transactivation potencies of polybrominated diphenyl ethers (PBDEs) using an in vitro bsPPARα reporter gene assay. BDE47, BDE99, and BDE153 induced bsPPARα-mediated transcriptional activities in a dose-dependent manner. To compare bsPPARα transactivation potencies of PBDEs, perfluorooctanoic acid (PFOA)-based relative potencies (REPs), a ratio of 50% effective concentration of PFOA to the test chemical, were determined. The order of REPs of PBDEs was BDE153 (13) > BDE99 (8.1) > BDE47 (6.6) > PFOA (1.0) > BDE100, BDE154, and BDE183 (not activated). PBDEs with two bromine atoms at the ortho position showed higher bsPPARα transactivation potencies than those with three bromine atoms. Comparison of the lowest-observed-effect concentration in bsPPARα reporter gene assays revealed that BDE99 was 7-fold more potent than CB99, a polychlorinated biphenyl congener with the same IUPAC number, indicating that brominated congeners could more efficiently activate bsPPARα than chlorinated congeners. The REPs of PBDEs for bsPPARα transactivation were approximately 7- to 13-fold higher than those of perfluorochemicals (PFCs), suggesting that the effects of PBDEs on the bsPPARα signaling pathway may be superior to those of PFCs. This study provides the first evidence that PBDE congeners activate PPARα in vitro.
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In Vitro Assessment of Activation of Baikal Seal (Pusa sibirica) Peroxisome Proliferator-Activated Receptor α by Polybrominated Diphenyl Ethers
2018Co-Authors: Hiroshi Ishibashi, Eun-young Kim, Koji Arizono, Hisato IwataAbstract:We investigated the Baikal Seal (Pusa sibirica) peroxisome proliferator-activated receptor α (bsPPARα) transactivation potencies of polybrominated diphenyl ethers (PBDEs) using an in vitro bsPPARα reporter gene assay. BDE47, BDE99, and BDE153 induced bsPPARα-mediated transcriptional activities in a dose-dependent manner. To compare bsPPARα transactivation potencies of PBDEs, perfluorooctanoic acid (PFOA)-based relative potencies (REPs), a ratio of 50% effective concentration of PFOA to the test chemical, were determined. The order of REPs of PBDEs was BDE153 (13) > BDE99 (8.1) > BDE47 (6.6) > PFOA (1.0) > BDE100, BDE154, and BDE183 (not activated). PBDEs with two bromine atoms at the ortho position showed higher bsPPARα transactivation potencies than those with three bromine atoms. Comparison of the lowest-observed-effect concentration in bsPPARα reporter gene assays revealed that BDE99 was 7-fold more potent than CB99, a polychlorinated biphenyl congener with the same IUPAC number, indicating that brominated congeners could more efficiently activate bsPPARα than chlorinated congeners. The REPs of PBDEs for bsPPARα transactivation were approximately 7- to 13-fold higher than those of perfluorochemicals (PFCs), suggesting that the effects of PBDEs on the bsPPARα signaling pathway may be superior to those of PFCs. This study provides the first evidence that PBDE congeners activate PPARα in vitro
Shinsuke Tanabe - One of the best experts on this subject based on the ideXlab platform.
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Analysis of Thyroid Hormones in Serum of Baikal Seals and Humans by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) and Immunoassay Methods: Application of the LC-MS/MS Method to Wildlife Tissues
2016Co-Authors: Tatsuya Kunisue, Akifumi Eguchi, Hisato Iwata, Shinsuke Tanabe, Kurunthachalam KannanAbstract:Thyroid hormones (THs) are essential for the regulation of growth and development in both humans and wildlife. Until recently, TH concentrations in the tissues of animals have been examined by immunoassay (IA) methods. IA methods are sensitive, but for TH analysis, they are compromised by a lack of adequate specificity. In this study, we determined the concentrations of six THs, l-thyroxine (T4), 3,3′,5-triiodo-l-thyronine (T3), 3,3′,5′-triiodo-l-thyronine (rT3), 3,5-diiodo-l-thyronine (3,5-T2), 3,3′-diiodo-l-thyronine (3,3′-T2), and 3-iodo-l-thyronine (3-T1), in the serum of humans (n = 79) and wild Baikal Seals (n = 37), by isotope ([13C6]-T4)-dilution liquid chromatography (LC)-tandem mass spectrometry (MS/MS), and compared the TH levels with those measured by an electrochemiluminescent immunoassay (ECLIA) method. T3 and T4 were detected in all serum samples of both humans and Baikal Seals, whereas T1, 3,3′-T2, and 3,5-T2 were below the limit of detection (LOD). rT3 was detected in Baikal Seal sera at concentrations higher than T3 in 28 Seal samples, indicating an anomaly in deiodinase activity in Baikal Seals. In humans, regression analyses of TH concentrations, measured by ECLIA and LC-MS/MS methods, showed significant correlations for T4 (r = 0.852) and T3 (r = 0.676; after removal of a serum sample with abnormal T3 levels). In Baikal Seals, a low correlation coefficient (r = 0.466) for T4 levels and no correlation for T3 levels (p = 0.093) were found between ECLIA and LC-MS/MS methods. These results suggest that interference by a nonspecific reaction against anti-T3 and anti-T4 antibodies used in the ECLIA can contribute to inaccuracies in TH measurement in Baikal Seals. When the relationship between concentrations of THs in sera and dioxin-like toxic equivalents in blubber samples of Baikal Seals (n = 19) was examined, a significantly negative correlation was found for serum T4 levels measured by the LC-MS/MS method, but not for those measured by ECLIA. Thus, our results indicate that the LC-MS/MS method is more reliable and accurate for the elucidation of alteration in circulating TH levels in wildlife, as caused by environmental and physiological factors
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In Vitro and in Silico Analyses for Predicting Hepatic Cytochrome P450-Dependent Metabolic Potencies of Polychlorinated Biphenyls in the Baikal Seal.
Environmental science & technology, 2015Co-Authors: Jean Yoo, Shinsuke Tanabe, Eun-young Kim, Masashi Hirano, Hazuki Mizukawa, Kei Nomiyama, Tetsuro Agusa, Hisato IwataAbstract:The aim of this study was to understand the cytochrome P450 (CYP)-dependent metabolic pathway and potency of polychlorinated biphenyls (PCBs) in the Baikal Seal (Pusa sibirica). In vitro metabolism of 62 PCB congener mixtures was investigated by using liver microsomes of this species. A decreased ratio of over 20% was observed for CB3, CB4, CB8, CB15, CB19, CB22, CB37, CB54, CB77, and CB105, suggesting the preferential metabolism of low-chlorinated PCBs by CYPs. The highly activated metabolic pathways in Baikal Seals that were predicted from the decreased PCBs and detected hydroxylated PCBs (OH-PCBs) were CB22 to 4'OH-CB20 and CB77 to 4'OH-CB79. The total amount of OH-PCBs detected as identified and unidentified congeners accounted for only a 3.8 ± 1.7 mol % of loaded PCBs, indicating many unknown PCB metabolic pathways. To explore factors involved in CYP-dependent PCB metabolism, we examined the relationships among the structural and physicochemical properties of PCBs, the in silico PCB-CYP docking parameters, and the in vitro PCB decreased ratios by principal component analysis. Statistical analysis showed that the decreased PCB ratio was at least partly accounted for by the substituted chlorine number of PCBs and the distance from the Cl-unsubstituted carbon of docked PCBs to the heme Fe in CYP2A and 2B.
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In Vitro and in Silico Analyses for Predicting Hepatic Cytochrome P450-Dependent Metabolic Potencies of Polychlorinated Biphenyls in the Baikal Seal
2015Co-Authors: Jean Yoo, Shinsuke Tanabe, Eun-young Kim, Masashi Hirano, Hazuki Mizukawa, Kei Nomiyama, Tetsuro Agusa, Hisato IwataAbstract:The aim of this study was to understand the cytochrome P450 (CYP)-dependent metabolic pathway and potency of polychlorinated biphenyls (PCBs) in the Baikal Seal (Pusa sibirica). In vitro metabolism of 62 PCB congener mixtures was investigated by using liver microsomes of this species. A decreased ratio of over 20% was observed for CB3, CB4, CB8, CB15, CB19, CB22, CB37, CB54, CB77, and CB105, suggesting the preferential metabolism of low-chlorinated PCBs by CYPs. The highly activated metabolic pathways in Baikal Seals that were predicted from the decreased PCBs and detected hydroxylated PCBs (OH-PCBs) were CB22 to 4′OH-CB20 and CB77 to 4′OH-CB79. The total amount of OH-PCBs detected as identified and unidentified congeners accounted for only a 3.8 ± 1.7 mol % of loaded PCBs, indicating many unknown PCB metabolic pathways. To explore factors involved in CYP-dependent PCB metabolism, we examined the relationships among the structural and physicochemical properties of PCBs, the in silico PCB-CYP docking parameters, and the in vitro PCB decreased ratios by principal component analysis. Statistical analysis showed that the decreased PCB ratio was at least partly accounted for by the substituted chlorine number of PCBs and the distance from the Cl-unsubstituted carbon of docked PCBs to the heme Fe in CYP2A and 2B
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Toxicological assessment of polychlorinated biphenyls and their metabolites in the liver of Baikal Seal (Pusa sibirica).
Environmental science & technology, 2014Co-Authors: Kei Nomiyama, Akifumi Eguchi, Hisato Iwata, Tatsuya Kunisue, Shusaku Hirakawa, Eun-young Kim, Jean Yoo, Chika Kanbara, Daisuke Imaeda, Shinsuke TanabeAbstract:We have previously reported that high accumulation of dioxins and related compounds induced cytochrome P450 (CYP 1s) isozymes in the liver of wild Baikal Seals, implying the enhanced hydroxylation of polychlorinated biphenyls (PCBs). The present study attempted to elucidate the residue concentrations and patterns of PCBs and hydroxylated PCBs (OH-PCBs) in the livers of Baikal Seals. The hepatic residue concentrations were used to assess the potential effects of PCBs and OH-PCBs in combination with the analyses of serum thyroid hormones, hepatic mRNA levels, and biochemical markers. The hepatic expression levels of CYP1 genes were positively correlated with the concentration of each OH-PCB congener. This suggests chronic induction of these CYP1 isozymes by exposure to PCBs and hydroxylation of PCBs induced by CYP 1s. Hepatic mRNA expression monitoring using a custom microarray showed that chronic exposure to PCBs and their metabolites alters the gene expression levels related to oxidative stress, iron ion ...
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analysis of thyroid hormones in serum of Baikal Seals and humans by liquid chromatography tandem mass spectrometry lc ms ms and immunoassay methods application of the lc ms ms method to wildlife tissues
Environmental Science & Technology, 2011Co-Authors: Tatsuya Kunisue, Akifumi Eguchi, Hisato Iwata, Shinsuke Tanabe, Kurunthachalam KannanAbstract:Thyroid hormones (THs) are essential for the regulation of growth and development in both humans and wildlife. Until recently, TH concentrations in the tissues of animals have been examined by immunoassay (IA) methods. IA methods are sensitive, but for TH analysis, they are compromised by a lack of adequate specificity. In this study, we determined the concentrations of six THs, l-thyroxine (T4), 3,3′,5-triiodo-l-thyronine (T3), 3,3′,5′-triiodo-l-thyronine (rT3), 3,5-diiodo-l-thyronine (3,5-T2), 3,3′-diiodo-l-thyronine (3,3′-T2), and 3-iodo-l-thyronine (3-T1), in the serum of humans (n = 79) and wild Baikal Seals (n = 37), by isotope ([13C6]-T4)-dilution liquid chromatography (LC)-tandem mass spectrometry (MS/MS), and compared the TH levels with those measured by an electrochemiluminescent immunoassay (ECLIA) method. T3 and T4 were detected in all serum samples of both humans and Baikal Seals, whereas T1, 3,3′-T2, and 3,5-T2 were below the limit of detection (LOD). rT3 was detected in Baikal Seal sera at ...
Eun-young Kim - One of the best experts on this subject based on the ideXlab platform.
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In vitro assessment of effects of persistent organic pollutants on the transactivation of estrogen receptor α and β (ERα and ERβ) from the Baikal Seal (Pusa sibirica)
Ecotoxicology and environmental safety, 2019Co-Authors: Yuka Yoshinouchi, Eun-young Kim, Masashi Hirano, Sachiko Shimizu, Jin-seon Lee, Ken-ichi Suzuki, Hisato IwataAbstract:Abstract To assess the effect of exposure to persistent organic pollutants (POPs) on the estrogen receptor (ER) signaling pathway in Baikal Seals (Pusa sibirica), we investigated the molecular characterizations and functions of two Baikal Seal ER (bsER) isoforms, bsERα and bsERβ. The bsERα and bsERβ cDNA clones isolated have an open reading frame of 595 and 530 amino acid residues, respectively. The tissue distribution analyses of bsER mRNAs showed that bsERα transcripts were primarily found in the ovary and uterus, and bsERβ in the muscle in wild Baikal Seals. The immunofluorescence staining assay showed that 17β-estradiol (E2) treatment promoted the nuclear translocation of in vitro-expressed bsERα. Transient transfection of bsERα in U2OS cells enhanced the transcription of pS2, an ER target gene of E2. We then measured bsER-mediated transactivation potencies of POPs in an in vitro reporter gene assay system, in which a bsERα or bsERβ expression vector was transfected into COS-1 cells. For comparison, transactivation potencies of POPs on mouse ERs (mERα and mERβ) were also evaluated in the same manner. Results showed significant dose-dependent responses of bsERs and mERs when treated with p,p’-dichlorodiphenyltrichloroethane (p,p’-DDT), and p,p’-dichlorodiphenyldichloroethylene (p,p’-DDE). bsERs and mERs showed no response when exposed to polychlorinated biphenyls (PCBs) or 2,3,7,8-tetrachlorodibenzo-p-dioxin. Comparison of the dose-response curves of DDTs across species (bsERs vs. mERs) showed that bsERα had a response similar to mERα, but bsERβ was less sensitive than mERβ. Comparing the lowest observable effective concentrations of p,p′-DDT (2.8 μM) and p,p′-DDE (10 μM) for in vitro bsERα-mediated transactivation with their hepatic concentrations in wild Baikal Seals indicated that some individuals accumulated these compounds at levels comparable to the effective concentrations, suggesting the potential disruption of the bsERα signaling pathway in the wild population by these compounds. Co-transfection experiments with bsER and the aryl hydrocarbon receptor (AHR) suggested that high accumulation of estrogenic compounds exerts a synergistic effect with dioxin-like congeners on ER signaling through AHR activation in the wild Seal population.
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In Vitro and In Silico Evaluations of Binding Affinities of Perfluoroalkyl Substances to Baikal Seal and Human Peroxisome Proliferator-Activated Receptor α
Environmental science & technology, 2019Co-Authors: Hiroshi Ishibashi, Eun-young Kim, Masashi Hirano, Hisato IwataAbstract:In this study, we assessed the binding affinities of perfluoroalkyl substances (PFASs), including perfluoroalkyl carboxylates (PFCAs) and perfluoroalkyl sulfonates (PFSAs), to the ligand-binding domains (LBDs) of Baikal Seal (Pusa sibirica; bs) and human (h) peroxisome proliferator-activated receptor alpha (PPARα). An in vitro competitive binding assay showed that six PFCAs and two PFSAs could bind to recombinant bs and hPPARα LBD proteins in a dose-dependent manner. The relative binding affinities (RBAs) of PFASs to bsPPARα were as follows: PFOS > PFDA > PFNA > PFUnDA > PFOA > PFHxS > PFHpA > PFHxA. The RBAs to bsPPARα showed a significant positive correlation with those to hPPARα. In silico PPARα homology modeling predicted that there were two ligand-binding pockets (LBPs) in the bsPPARα and hPPARα LBDs. Structure–activity relationship analyses suggested that the binding potencies of PFASs to PPARα might depend on LBP binding cavity volume, hydrogen bond interactions, the number of perfluorinated carbon...
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In Vitro and In Silico Evaluations of Binding Affinities of Perfluoroalkyl Substances to Baikal Seal and Human Peroxisome Proliferator-Activated Receptor α
2019Co-Authors: Hiroshi Ishibashi, Eun-young Kim, Masashi Hirano, Hisato IwataAbstract:In this study, we assessed the binding affinities of perfluoroalkyl substances (PFASs), including perfluoroalkyl carboxylates (PFCAs) and perfluoroalkyl sulfonates (PFSAs), to the ligand-binding domains (LBDs) of Baikal Seal (Pusa sibirica; bs) and human (h) peroxisome proliferator-activated receptor alpha (PPARα). An in vitro competitive binding assay showed that six PFCAs and two PFSAs could bind to recombinant bs and hPPARα LBD proteins in a dose-dependent manner. The relative binding affinities (RBAs) of PFASs to bsPPARα were as follows: PFOS > PFDA > PFNA > PFUnDA > PFOA > PFHxS > PFHpA > PFHxA. The RBAs to bsPPARα showed a significant positive correlation with those to hPPARα. In silico PPARα homology modeling predicted that there were two ligand-binding pockets (LBPs) in the bsPPARα and hPPARα LBDs. Structure–activity relationship analyses suggested that the binding potencies of PFASs to PPARα might depend on LBP binding cavity volume, hydrogen bond interactions, the number of perfluorinated carbons, and the hydrophobicity of PFASs. Interspecies comparison of the in vitro binding affinities revealed that bsPPARα had higher preference for PFASs with long carbon chains than hPPARα. The in silico docking simulations suggested that the first LBP of bsPPARα had higher affinities than that of hPPARα; however, the second LBP of bsPPARα had lower affinities than that of hPPARα. To our knowledge, this is the first evidence showing interspecies differences in the binding of PFASs to PPARαs and their structure–activity relationships
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In Vitro Assessment of Activation of Baikal Seal ( Pusa sibirica) Peroxisome Proliferator-Activated Receptor α by Polybrominated Diphenyl Ethers.
Environmental science & technology, 2018Co-Authors: Hiroshi Ishibashi, Eun-young Kim, Koji Arizono, Hisato IwataAbstract:We investigated the Baikal Seal ( Pusa sibirica) peroxisome proliferator-activated receptor α (bsPPARα) transactivation potencies of polybrominated diphenyl ethers (PBDEs) using an in vitro bsPPARα reporter gene assay. BDE47, BDE99, and BDE153 induced bsPPARα-mediated transcriptional activities in a dose-dependent manner. To compare bsPPARα transactivation potencies of PBDEs, perfluorooctanoic acid (PFOA)-based relative potencies (REPs), a ratio of 50% effective concentration of PFOA to the test chemical, were determined. The order of REPs of PBDEs was BDE153 (13) > BDE99 (8.1) > BDE47 (6.6) > PFOA (1.0) > BDE100, BDE154, and BDE183 (not activated). PBDEs with two bromine atoms at the ortho position showed higher bsPPARα transactivation potencies than those with three bromine atoms. Comparison of the lowest-observed-effect concentration in bsPPARα reporter gene assays revealed that BDE99 was 7-fold more potent than CB99, a polychlorinated biphenyl congener with the same IUPAC number, indicating that brominated congeners could more efficiently activate bsPPARα than chlorinated congeners. The REPs of PBDEs for bsPPARα transactivation were approximately 7- to 13-fold higher than those of perfluorochemicals (PFCs), suggesting that the effects of PBDEs on the bsPPARα signaling pathway may be superior to those of PFCs. This study provides the first evidence that PBDE congeners activate PPARα in vitro.
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In Vitro Assessment of Activation of Baikal Seal (Pusa sibirica) Peroxisome Proliferator-Activated Receptor α by Polybrominated Diphenyl Ethers
2018Co-Authors: Hiroshi Ishibashi, Eun-young Kim, Koji Arizono, Hisato IwataAbstract:We investigated the Baikal Seal (Pusa sibirica) peroxisome proliferator-activated receptor α (bsPPARα) transactivation potencies of polybrominated diphenyl ethers (PBDEs) using an in vitro bsPPARα reporter gene assay. BDE47, BDE99, and BDE153 induced bsPPARα-mediated transcriptional activities in a dose-dependent manner. To compare bsPPARα transactivation potencies of PBDEs, perfluorooctanoic acid (PFOA)-based relative potencies (REPs), a ratio of 50% effective concentration of PFOA to the test chemical, were determined. The order of REPs of PBDEs was BDE153 (13) > BDE99 (8.1) > BDE47 (6.6) > PFOA (1.0) > BDE100, BDE154, and BDE183 (not activated). PBDEs with two bromine atoms at the ortho position showed higher bsPPARα transactivation potencies than those with three bromine atoms. Comparison of the lowest-observed-effect concentration in bsPPARα reporter gene assays revealed that BDE99 was 7-fold more potent than CB99, a polychlorinated biphenyl congener with the same IUPAC number, indicating that brominated congeners could more efficiently activate bsPPARα than chlorinated congeners. The REPs of PBDEs for bsPPARα transactivation were approximately 7- to 13-fold higher than those of perfluorochemicals (PFCs), suggesting that the effects of PBDEs on the bsPPARα signaling pathway may be superior to those of PFCs. This study provides the first evidence that PBDE congeners activate PPARα in vitro
Nobuyuki Miyazaki - One of the best experts on this subject based on the ideXlab platform.
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Baikal Seal: Pusa sibirica
Encyclopedia of Marine Mammals, 2018Co-Authors: Nobuyuki MiyazakiAbstract:Summary The Baikal Seal, endemic to Lake Baikal, was derived from a ringed Seal ancestor in the Arctic Ocean approximately 400 thousand years ago, as opposed to being a Paratethys relict. Males and females of this small, true Seal species look very similar, but adult males are slightly larger than adult females. They are one of a few freshwater pinniped species. Baikal Seals have been hunted for thousands of years and remain an important local resource. Recent viral outbreaks are a concern, but the population is thought to be at the lake’s carrying capacity and numbers over 100,000.
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Caspian and Baikal Seals: Pusa caspica and Pusa sibirica
Encyclopedia of Marine Mammals, 2009Co-Authors: Nobuyuki MiyazakiAbstract:Publisher Summary This chapter discusses the characteristics, taxonomy, distribution, abundance, and ecology of Baikal Seals (Pusa sibirica) and Caspian Seals (P. caspica). Baikal Seals (Pusa sibirica) and Caspian Seals (P. caspica) have common features such as small size, delicate skull, and affinity for ice. Based on mtDNA haplotypes, Caspian Seals were derived from the common ancient type of Pusa 60 million years ago and were subsequently isolated in the Caspian Sea. Baikal Seals were derived from a ringed-Seal-like ancestor in the Arctic Ocean and isolated in Lake Baikal 40 million years ago. Baikal Seals feed mainly on four fish species: the greater golomyanka (Comephorus baicalensis), the lesser golomyanka (C. dybowskii), the Baikal yellowfin sculpin (Cottocomephorus grewingki), and the longfin sculpin (C. comephoroides), all of which are not of commercial value. In captivity, an adult Baikal Seal consumes up to 5.6 kg of fish per day. Based on data obtained by Argos satellite-linked transmitters, most dives of Baikal Seals are to depths of 10–50 m, although a few dives exceed 300 m.
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contamination and effects of perfluorochemicals in Baikal Seal pusa sibirica 1 residue level tissue distribution and temporal trend
Environmental Science & Technology, 2008Co-Authors: Hiroshi Ishibashi, Hisato Iwata, Shinsuke Tanabe, Kurunthachalam Kannan, Masao Amano, Nobuyuki Miyazaki, Eun-young Kim, Lin Tao, Valeriy Batoev, Evgeny A. PetrovAbstract:Concentrations of perfluorochemicals (PFCs) including perfluoroalkylsulfonates (PFSAs) and perfluoroalkylcarboxylates (PFCAs) were determined in liver and serum of Baikal Seals (Pusa sibirica) collected from Lake Baikal, Russia in 2005. Among the 10 PFC compounds measured, perfluorononanoic acid (PFNA, 3.3–72 ng/g wet wt) concentrations were the highest in liver, followed by perfluorooctanesulfonate (PFOS, 2.6–38 ng/g). The accumulation profile of long-chain (C7-C12) PFCAs in particular, the predominance of PFNA, indicated that 8:2 fluorotelomer alcohol or commercially manufactured PFNA is a major local source of PFCs in Lake Baikal. No gender-related differences in the concentrations of individual PFCs or total PFCs were found. Tissues from pups and juveniles contained relatively higher concentrations of PFCs than tissues from subadults and adults, suggesting that maternal transfer of PFCs is of critical importance. Comparison of concentrations of PFCs in livers and sera collected from the same individua...
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molecular characterization of cytochrome p450 1a1 1a2 and 1b1 and effects of polychlorinated dibenzo p dioxin dibenzofuran and biphenyl congeners on their hepatic expression in Baikal Seal pusa sibirica
Toxicological Sciences, 2007Co-Authors: Shusaku Hirakawa, Evgeny A. Petrov, Hisato Iwata, Yoko Takeshita, Tomohiro Sakamoto, Yuka Okajima, Masao Amano, Nobuyuki Miyazaki, Shinsuke TanabeAbstract:This study attempts to relate the 2,3,7,8-tetrachlorodibenzo-pdioxin toxic equivalent (TEQ) level with certain responses including the catalytic activities and expression of hepatic cytochrome P450 (CYP) 1A and CYP1B in wild population of Baikal Seal (Pusa sibirica). We isolated full-length CYP1A1, 1A2, and 1B1 cDNAs, which encode proteins of 516, 512, and 543 amino acids, respectively. Immunochemical analysis demonstrated that a cross-reactive protein with polyclonal antibody against rat CYP1A1 or CYP1B1 was detected in the Seal liver. Total TEQ levels showed significant positive correlations with expression levels of CYP1A1, 1A2, and 1B1 mRNAs, and further with both CYP1A- and CYP1B-like proteins, indicating chronic induction of these CYP isozymes by TEQs. The 50% effective concentration for CYP1Alike protein induction was estimated to be 65 pg TEQ/g wet weight. To evaluate the potential of congener-specific metabolism, profiles of negative correlations between the concentrations of eachcongener normalized to a relatively recalcitrant congener, PCB169, and CYP1A-like protein levels were also estimated. Significant negative correlations of 2,3,7,8-tetrachlorodibenzofuran and PCB77 to CYP1A-like protein expression may possibly be due to the preferential metabolism of these congeners. Anti-rat CYP1A1 and CYP1B1 antisera equivalently inhibited ethoxyresorufin Odeethylase (EROD) activity in the Seal microsomes, suggesting that both CYPs are involved in EROD activity. Hepatic EROD revealed an increasing trend at lower TEQs, but a declining trend at higher levels, implying a catalytic inhibition of CYP1A and CYP1B. Furthermore, ratios of CYP1B1/CYP1A1 mRNA expression levels increased with TEQs, indicating the enhanced risk of carcinogenicity by preferential induction of CYP1B1 by TEQs in the liver. Key Words: Baikal Seal; toxic equivalent; cytochrome P450 1A; cytochrome P450 1B; catalytic inhibition. Planar halogenated aromatic hydrocarbons (PHAHs) such as polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (Co-PCBs) are ubiquitous contaminants. These compounds are biomagnified in the food web due to their lipophilic and persistent properties. PHAHs are notably accumulated in a variety of aquatic species (Tanabe et al., 1994). Aquatic mammals may be at high risk to PHAHs, as suggested by high incidence of mass mortalities since the 1970s. The accumulation of PHAHs in aquatic mammals has been considered as a contributing factor in the epizootic, although the direct cause for this outbreak was infectious diseases (de Swart etal., 1995). However, the magnitude of effects that these chemicals pose to aquatic mammals remains uncertain because of the lack of direct investigation linking between PHAH contamination levels and certain biochemical/toxicological evidences. The mechanisms of toxic effects by PHAHs in aquatic mammals still remain unclear, but are likely to involve the aryl hydrocarbon receptor (AHR)-signaling pathway in rodents and
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Molecular characterization of cytochrome P450 1A1, 1A2, and 1B1, and effects of polychlorinated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners on their hepatic expression in Baikal Seal (Pusa sibirica).
Toxicological sciences : an official journal of the Society of Toxicology, 2007Co-Authors: Shusaku Hirakawa, Evgeny A. Petrov, Hisato Iwata, Yoko Takeshita, Tomohiro Sakamoto, Yuka Okajima, Masao Amano, Nobuyuki Miyazaki, Eun-young Kim, Shinsuke TanabeAbstract:This study attempts to relate the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalent (TEQ) level with certain responses including the catalytic activities and expression of hepatic cytochrome P450 (CYP) 1A and CYP1B in wild population of Baikal Seal (Pusa sibirica). We isolated full-length CYP1A1, 1A2, and 1B1 cDNAs, which encode proteins of 516, 512, and 543 amino acids, respectively. Immunochemical analysis demonstrated that a cross-reactive protein with polyclonal antibody against rat CYP1A1 or CYP1B1 was detected in the Seal liver. Total TEQ levels showed significant positive correlations with expression levels of CYP1A1, 1A2, and 1B1 mRNAs, and further with both CYP1A- and CYP1B-like proteins, indicating chronic induction of these CYP isozymes by TEQs. The 50% effective concentration for CYP1A-like protein induction was estimated to be 65 pg TEQ/g wet weight. To evaluate the potential of congener-specific metabolism, profiles of negative correlations between the concentrations of eachcongener normalized to a relatively recalcitrant congener, PCB169, and CYP1A-like protein levels were also estimated. Significant negative correlations of 2,3,7,8-tetrachlorodibenzofuran and PCB77 to CYP1A-like protein expression may possibly be due to the preferential metabolism of these congeners. Anti-rat CYP1A1 and CYP1B1 antisera equivalently inhibited ethoxyresorufin O-deethylase (EROD) activity in the Seal microsomes, suggesting that both CYPs are involved in EROD activity. Hepatic EROD revealed an increasing trend at lower TEQs, but a declining trend at higher levels, implying a catalytic inhibition of CYP1A and CYP1B. Furthermore, ratios of CYP1B1/CYP1A1 mRNA expression levels increased with TEQs, indicating the enhanced risk of carcinogenicity by preferential induction of CYP1B1 by TEQs in the liver.
Alexander S. Graphodatsky - One of the best experts on this subject based on the ideXlab platform.
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The Ancestral Carnivore Karyotype As Substantiated by Comparative Chromosome Painting of Three Pinnipeds, the Walrus, the Steller Sea Lion and the Baikal Seal (Pinnipedia, Carnivora).
PLOS ONE, 2016Co-Authors: Violetta R Beklemisheva, Vladimir N Burkanov, Natalia A. Lemskaya, Anastasia I. Kulemzina, Polina L Perelman, Anastasia A. Proskuryakova, Alexander S. GraphodatskyAbstract:Karyotype evolution in Carnivora is thoroughly studied by classical and molecular cytogenetics and supplemented by reconstructions of Ancestral Carnivora Karyotype (ACK). However chromosome painting information from two pinniped families (Odobenidae and Otariidae) is noticeably missing. We report on the construction of the comparative chromosome map for species from each of the three pinniped families: the walrus (Odobenus rosmarus, Odobenidae–monotypic family), near threatened Steller sea lion (Eumetopias jubatus, Otariidae) and the endemic Baikal Seal (Pusa sibirica, Phocidae) using combination of human, domestic dog and stone marten whole-chromosome painting probes. The earliest karyological studies of Pinnipedia showed that pinnipeds were characterized by a pronounced karyological conservatism that is confirmed here with species from Phocidae, Otariidae and Odobenidae sharing same low number of conserved human autosomal segments (32). Chromosome painting in Pinnipedia and comparison with non-pinniped carnivore karyotypes provide strong support for refined structure of ACK with 2n = 38. Constructed comparative chromosome maps show that pinniped karyotype evolution was characterized by few tandem fusions, seemingly absent inversions and slow rate of genome rearrangements (less then one rearrangement per 10 million years). Integrative comparative analyses with published chromosome painting of Phoca vitulina revealed common cytogenetic signature for Phoca/Pusa branch and supports Phocidae and Otaroidea (Otariidae/Odobenidae) as sister groups. We revealed rearrangements specific for walrus karyotype and found the chromosomal signature linking together families Otariidae and Odobenidae. The Steller sea lion karyotype is the most conserved among three studied species and differs from the ACK by single fusion. The study underlined the strikingly slow karyotype evolution of the Pinnipedia in general and the Otariidae in particular.
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The Ancestral Carnivore Karyotype As Substantiated by Comparative Chromosome Painting of Three Pinnipeds, the Walrus, the Steller Sea Lion and the Baikal Seal (Pinnipedia, Carnivora) - Table 1
2016Co-Authors: Violetta R Beklemisheva, Vladimir N Burkanov, Natalia A. Lemskaya, Anastasia I. Kulemzina, Polina L Perelman, Anastasia A. Proskuryakova, Alexander S. GraphodatskyAbstract:The Ancestral Carnivore Karyotype As Substantiated by Comparative Chromosome Painting of Three Pinnipeds, the Walrus, the Steller Sea Lion and the Baikal Seal (Pinnipedia, Carnivora) - Table
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Correspondence of pinniped (the Steller sea lion, the walrus, the Baikal Seal and the common Seal1) chromosomes with dog, human, ancestral carnivore karyotype (ACK2), stone marten3 and cat3 chromosomes.
2016Co-Authors: Violetta R Beklemisheva, Vladimir N Burkanov, Natalia A. Lemskaya, Anastasia I. Kulemzina, Polina L Perelman, Anastasia A. Proskuryakova, Alexander S. GraphodatskyAbstract:Correspondence of pinniped (the Steller sea lion, the walrus, the Baikal Seal and the common Seal1) chromosomes with dog, human, ancestral carnivore karyotype (ACK2), stone marten3 and cat3 chromosomes.
