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Article ; Online: Binding profiles of human and mouse complement component 8γ to trisubstituted organometallic compounds.

Yamamoto, Katsuya / Matsumaru, Daisuke / Ishida, Keishi / Endo, Satoshi / Hiromori, Youhei / Nakanishi, Tsuyoshi

2024 Volume 395, Page(s) 110998

Abstract: Complement component 8gamma (C8γ), a member of the lipocalin protein family, is suggested to act as a carrier protein for various chemicals. Although C8γ has been identified in both humans and rodents for some time, our understanding of the species ... ...

Abstract	Complement component 8gamma (C8γ), a member of the lipocalin protein family, is suggested to act as a carrier protein for various chemicals. Although C8γ has been identified in both humans and rodents for some time, our understanding of the species differences in its chemical binding properties remains limited. In the present study, with the aim to elucidate the potential role of C8γ as a carrier protein in both humans and mice, we conducted a radioligand binding assay to examine the chemical binding properties of human C8γ (hC8γ) and mouse C8γ (mC8γ). Scatchard analysis revealed that [
Language	English
Publishing date	2024-04-16
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	218799-1
ISSN	1872-7786 ; 0009-2797
ISSN (online)	1872-7786
ISSN	0009-2797
DOI	10.1016/j.cbi.2024.110998
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Zs.A 686: Show issues

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Article ; Online: Evaluation of the Estrogenic Action Potential of Royal Jelly by Genomic Signaling Pathway in Vitro and in Vivo.

Ishida, Keishi / Matsumaru, Daisuke / Shimizu, Shinya / Hiromori, Youhei / Nagase, Hisamitsu / Nakanishi, Tsuyoshi

Biological & pharmaceutical bulletin

2022 Volume 45, Issue 10, Page(s) 1510–1517

Abstract: Royal jelly (RJ) has beneficial effects on human health, and some of these effects are reported to be the result of its estrogenic activity; however, chemicals with estrogenic activities may disrupt physiological estrogen signaling leading to adverse ... ...

Abstract	Royal jelly (RJ) has beneficial effects on human health, and some of these effects are reported to be the result of its estrogenic activity; however, chemicals with estrogenic activities may disrupt physiological estrogen signaling leading to adverse effects on human health. Thus, clarification of the mode of action of RJ is needed. Here, we investigated whether the estrogen-like actions of RJ are induced via estrogen receptors (ERs)-mediated genomic actions by using an in vitro reporter assay in human choriocarcinoma JEG3 cells and an estrogen-responsive reporter (E-Rep) mouse line that can be used to sensitively detect transactivation of ERs in multiple organs simultaneously. In the in vitro reporter assay, ERs-dependent transcriptional activity was significantly increased by 17β-estradiol (E2) treatment at concentrations of 1 nM and above, confirming that the assay was highly responsive to estrogen; however, RJ did not exhibit any agonist activity via either the α or β form of ER. Similarly, in E-Rep mice, E2 showed significant ERs-dependent genomic action in 17 tissue types including uterus and mammary gland, whereas RJ did not. Thus, unlike endocrine-disrupting chemicals, the estrogen-like activity of RJ is unlikely to be due to genomic actions via ERs.
MeSH term(s)	Action Potentials ; Animals ; Cell Line, Tumor ; Estradiol/metabolism ; Estrogen Receptor alpha ; Estrogens/pharmacology ; Fatty Acids ; Female ; Genomics ; Humans ; Mice ; Receptors, Estrogen/genetics ; Receptors, Estrogen/metabolism ; Signal Transduction
Chemical Substances	Estrogen Receptor alpha ; Estrogens ; Fatty Acids ; Receptors, Estrogen ; Estradiol (4TI98Z838E) ; royal jelly (L497I37F0C)
Language	English
Publishing date	2022-08-02
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1150271-x
ISSN	1347-5215 ; 0918-6158
ISSN (online)	1347-5215
ISSN	0918-6158
DOI	10.1248/bpb.b22-00383
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1474: Show issues

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Article ; Online: Evaluation of the Skin-Sensitizing Potential of Brazilian Green Propolis.

Shiraishi, Erina / Ishida, Keishi / Matsumaru, Daisuke / Ido, Akiko / Hiromori, Youhei / Nagase, Hisamitsu / Nakanishi, Tsuyoshi

International journal of molecular sciences

2021 Volume 22, Issue 24

Abstract: Propolis is a resinous mixture produced by bees from their secretions and plant material, so its composition varies depending on its botanical origin. Propolis has several beneficial bioactivities, but its skin sensitization properties have long been ... ...

Abstract	Propolis is a resinous mixture produced by bees from their secretions and plant material, so its composition varies depending on its botanical origin. Propolis has several beneficial bioactivities, but its skin sensitization properties have long been suspected. Nevertheless, the skin sensitization potency of Brazilian green propolis (BGP) has not been scientifically evaluated. Here, we used scientifically reliable tests to evaluate it. In vitro antigenicity test based on the human cell line activation test (OECD TG 442E) was performed by measuring the expression of CD54 and CD86, which are indicators of the antigenicity of test substances, on THP-1 and DC2.4 cells. BGP did not affect the expression of either marker on THP-1 cells, but upregulated the expression of CD86 on DC2.4 cells, suggesting that BGP may be a skin sensitizer. Then, we performed local lymph node assay (LLNA, OECD TG 429) as a definitive in vivo test. LLNA showed that 1.70% BGP primed skin sensitization and is a "moderate sensitizer". Our results indicate scientific proof of the validity of arbitrary concentrations (1-2%), which have been used empirically, and provide the first scientific information on the safe use of BGP.
MeSH term(s)	Allergens ; Animals ; Brazil ; Cell Line ; Dermatitis, Allergic Contact ; Female ; Humans ; Local Lymph Node Assay ; Mice ; Propolis/pharmacology ; Skin/drug effects ; THP-1 Cells
Chemical Substances	Allergens ; Propolis (9009-62-5)
Language	English
Publishing date	2021-12-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms222413538
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Article ; Online: Novel, highly sensitive, in vivo screening method detects estrogenic activity at low doses of bisphenol A.

Ishida, Keishi / Furukawa, Motoshi / Kunitani, Masataka / Yamagiwa, Rai / Hiromori, Youhei / Matsumaru, Daisuke / Hu, Jianying / Nagase, Hisamitsu / Nakanishi, Tsuyoshi

Journal of hazardous materials

2022 Volume 445, Page(s) 130461

Abstract: Low doses of bisphenol A (BPA), a typical endocrine-disrupting chemical (EDC), have been reported to exhibit estrogenic action in animals; however, the effects have not been fully clarified because of their non-reproducibility. Here, we developed a novel, ...

Abstract	Low doses of bisphenol A (BPA), a typical endocrine-disrupting chemical (EDC), have been reported to exhibit estrogenic action in animals; however, the effects have not been fully clarified because of their non-reproducibility. Here, we developed a novel, short-term screening test for estrogen-like chemicals using in vivo bioluminescence imaging of estrogen-responsive reporter (E-Rep) mice. Comparative studies using 17α-ethinylestradiol and selective estrogen receptor modulators demonstrated that the method provides higher detection sensitivity and requires less time than the uterotrophic bioassay, a well-established, in vivo screening method for estrogen-like chemicals. Our method could detect the estrogenic effects of BPA at doses below tolerable daily intakes, whereas the uterotrophic bioassay could not. Our results indicated that in vivo bioluminescence imaging using E-Rep mice was extremely useful for screening estrogenic chemicals and detecting estrogenic effects at low doses of EDCs, including BPA. Our method should help resolve the controversy about low-dose effects of EDCs.
Language	English
Publishing date	2022-11-23
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1491302-1
ISSN	1873-3336 ; 0304-3894
ISSN (online)	1873-3336
ISSN	0304-3894
DOI	10.1016/j.jhazmat.2022.130461
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Article: Discovery of contaminants with antagonistic activity against retinoic acid receptor in house dust

Jia, Yingting / Zhang, Hong / Hu, Wenxin / Wang, Lei / Kang, Qiyue / Liu, Jiaying / Nakanishi, Tsuyoshi / Hiromori, Youhei / Kimura, Tomoki / Tao, Shu / Hu, Jianying

Journal of hazardous materials. 2022 Mar. 15, v. 426

2022

Abstract: Retinoic acid receptors (RARs) control reproduction and development in vertebrates, but little attention has been paid to anthropogenic chemicals exhibiting RAR agoniztic/antagonistic activity. Here we applied a His-RARα pull-down assay combined with ... ...

Abstract	Retinoic acid receptors (RARs) control reproduction and development in vertebrates, but little attention has been paid to anthropogenic chemicals exhibiting RAR agoniztic/antagonistic activity. Here we applied a His-RARα pull-down assay combined with high-resolution mass spectrometry to identify chemicals with RARα activity in house dust. After screening, a total of 540 peaks were retained as potential RARα ligands. The mass spectra of 14 chemicals matched with those in the database, of which triphenyl phosphate, galaxolidone, di(2-ethylhexyl) phthalate (DEHP), tris(2-ethylhexyl) phosphate (TEHP), and tris(2-butoxyethyl) phosphate were confirmed by their standards. While one chemical in the sample matched with monophenyl phosphate in the MS/MS database, its retention time was much higher than that of monophenyl phosphate standard, suggesting that it may be an in-source fragment. Its parent ion was finally identified to be m/z 399.2663 using a similarity analysis among chromatographic peaks of hundreds of ions at the same retention time in MS¹ spectrum, and bis(2-ethylhexyl) phenyl phosphate (BEHPP) was identified. BEHPP, DEHP, and TEHP were for the first time identified to be RARα antagonists with IC₅₀ values of 6556, 6600, and 2538 nM, respectively. This study improved structural annotation and filled the knowledge gap regarding widespread environmental contaminants with RAR antagonistic activity.
Keywords	chromatography ; databases ; dust ; ligands ; phosphates ; phthalates ; pollution ; reproduction ; retinoic acid ; retinoic acid receptors
Language	English
Dates of publication	2022-0315
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	1491302-1
ISSN	1873-3336 ; 0304-3894
ISSN (online)	1873-3336
ISSN	0304-3894
DOI	10.1016/j.jhazmat.2021.127847
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Article ; Online: Alginate-coated activated charcoal enhances fecal excretion of 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice, with fewer side effects than uncoated one.

Dungkokkruad, Pinyapach / Tomita, Shunsuke / Hiromori, Youhei / Ishida, Keishi / Matsumaru, Daisuke / Mekada, Kyoko / Nagase, Hisamitsu / Tanaka, Keiichi / Nakanishi, Tsuyoshi

The Journal of toxicological sciences

2021 Volume 46, Issue 8, Page(s) 379–389

Abstract: Activated charcoal (AC) is a potential candidate antidote against dioxins. However, it is difficult to take AC as a supplement on a daily basis, because its long-term ingestion causes side effects such as constipation and deficiency of fat-soluble ... ...

Abstract	Activated charcoal (AC) is a potential candidate antidote against dioxins. However, it is difficult to take AC as a supplement on a daily basis, because its long-term ingestion causes side effects such as constipation and deficiency of fat-soluble essential nutrients and hypocholesterolemia. Alginate-coated AC, termed Health Carbon (HC), was developed to decrease the side effects of AC, but its pharmacological effects, including side effects, remains unclear. Here, we show that HC enhanced fecal excretion of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and decreased some side effects of unmodified AC, such as hypocholesterolemia, in male mice. Basal diet mixed with HC or unmodified AC at various concentrations was fed to mice for 16 days following a single intraperitoneal administration of [
MeSH term(s)	Administration, Oral ; Alginates/administration & dosage ; Animals ; Antidotes/administration & dosage ; Antidotes/adverse effects ; Antidotes/pharmacology ; Charcoal/administration & dosage ; Charcoal/adverse effects ; Charcoal/pharmacology ; Cholesterol/blood ; Constipation/chemically induced ; Feces ; Male ; Mice, Inbred Strains ; Polychlorinated Dibenzodioxins/metabolism ; Weight Loss ; Mice
Chemical Substances	Alginates ; Antidotes ; Polychlorinated Dibenzodioxins ; Charcoal (16291-96-6) ; Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2021-08-01
Publishing country	Japan
Document type	Journal Article
ZDB-ID	770623-6
ISSN	1880-3989 ; 0388-1350
ISSN (online)	1880-3989
ISSN	0388-1350
DOI	10.2131/jts.46.379
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Zs.A 1682: Show issues

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Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Tri-substituted organotin compounds, but not retinoic acid, are potent ligands of complement component 8 γ.

Yamamoto, Katsuya / Hiromori, Youhei / Matsumaru, Daisuke / Ishii, Yoichiro / Takeshita, Yuki / Tsubakihara, Iori / Kimura, Tomoki / Nagase, Hisamitsu / Nakanishi, Tsuyoshi

The Journal of toxicological sciences

2020 Volume 45, Issue 9, Page(s) 581–587

Abstract: Complement component 8 γ (C8γ) is a subunit of complement protein 8 (C8), which itself is a subunit of the complement cytolytic membrane attack complex. However, C8γ is also suggested to be a carrier protein for the general clearance of endogenous and ... ...

Abstract	Complement component 8 γ (C8γ) is a subunit of complement protein 8 (C8), which itself is a subunit of the complement cytolytic membrane attack complex. However, C8γ is also suggested to be a carrier protein for the general clearance of endogenous and exogenous compounds because it belongs to the lipocalin family of small secreted proteins that have the common ability to bind small hydrophobic ligands. Although retinoic acid, a metabolite of vitamin A, has been suggested as a potential ligand of C8γ, it remains unclear which other substances are able to bind to C8γ as ligands. Here, we evaluated the binding affinity of several organotin compounds that are ligands of a receptor of retinoic acid, retinoid X receptor, by using radioligand binding assays. The amount of [
MeSH term(s)	Binding, Competitive ; Carrier Proteins ; Complement C8 ; Complement Membrane Attack Complex/chemistry ; Ligands ; Organotin Compounds/toxicity ; Protein Binding ; Retinoid X Receptors/metabolism ; Tretinoin ; Trialkyltin Compounds/toxicity
Chemical Substances	Carrier Proteins ; Complement C8 ; Complement Membrane Attack Complex ; Ligands ; Organotin Compounds ; Retinoid X Receptors ; Trialkyltin Compounds ; tributyltin (4XDX163P3D) ; Tretinoin (5688UTC01R) ; triphenyltin (95T92AGN0V)
Language	English
Publishing date	2020-09-02
Publishing country	Japan
Document type	Journal Article
ZDB-ID	770623-6
ISSN	1880-3989 ; 0388-1350
ISSN (online)	1880-3989
ISSN	0388-1350
DOI	10.2131/jts.45.581
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1682: Show issues

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Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article: In vivo profiling of 2,3,7,8-tetrachlorodibenzo-p-dioxin–induced estrogenic/anti-estrogenic effects in female estrogen-responsive reporter transgenic mice

Yoshida, Ichiro / Ishida, Keishi / Yoshikawa, Hiroshi / Kitamura, Sho / Hiromori, Youhei / Nishioka, Yasushi / Ido, Akiko / Kimura, Tomoki / Nishikawa, Jun-ichi / Hu, Jianying / Nagase, Hisamitsu / Nakanishi, Tsuyoshi

Journal of hazardous materials. 2020 Mar. 05, v. 385

2020

Abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), commonly referred to simply as “dioxin”, is a persistent environmental pollutant. Because of its high environmental persistence and biological accumulation, humans and animals are often exposed to TCDD. ... ...

Abstract	2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), commonly referred to simply as “dioxin”, is a persistent environmental pollutant. Because of its high environmental persistence and biological accumulation, humans and animals are often exposed to TCDD. Therefore, the harmful effects on humans and animals is a major concern. Although studies have elucidated the adverse estrogenic and anti-estrogenic effects of TCDD, it is unclear in which tissues TCDD exerts these effects in vivo. To investigate the estrogen-related effects of TCDD in various tissues, we generated an improved estrogen-responsive reporter transgenic mouse in which the luciferase gene luc2 is expressed in response to estrogenic signals. Using these mice, we clarified that TCDD inhibits estrogenic signaling in liver and kidney but enhances estrogenic signaling in the pituitary gland in the same individual. Expression of aryl hydrocarbon receptor, aryl hydrocarbon receptor nuclear translocator, and estrogen receptor alpha mRNA was detected in liver, kidney, and pituitary gland, suggesting that the effects of TCDD on estrogenic signaling in these organs is independent of the expression pattern of these receptors. Thus, our results indicate that TCDD exerts both estrogenic and anti-estrogenic tissue-specific effects within the same individual.
Keywords	aromatic compounds ; environmental fate ; estrogen receptors ; females ; genes ; humans ; kidneys ; liver ; luciferase ; messenger RNA ; mice ; pituitary gland ; pollutants ; tetrachlorodibenzo-p-dioxin ; tissues ; transgenic animals
Language	English
Dates of publication	2020-0305
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	1491302-1
ISSN	1873-3336 ; 0304-3894
ISSN (online)	1873-3336
ISSN	0304-3894
DOI	10.1016/j.jhazmat.2019.121526
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Article ; Online: An Orthologue of the Retinoic Acid Receptor (RAR) Is Present in the Ecdysozoa Phylum Priapulida.

Fonseca, Elza S S / Hiromori, Youhei / Kaite, Yoshifumi / Ruivo, Raquel / Franco, João N / Nakanishi, Tsuyoshi / Santos, Miguel M / Castro, L Filipe C

Genes

2019 Volume 10, Issue 12

Abstract: Signalling molecules and their cognate receptors are central components of the Metazoa endocrine system. Defining their presence or absence in extant animal lineages is critical to accurately devise evolutionary patterns, physiological shifts and the ... ...

Abstract	Signalling molecules and their cognate receptors are central components of the Metazoa endocrine system. Defining their presence or absence in extant animal lineages is critical to accurately devise evolutionary patterns, physiological shifts and the impact of endocrine disrupting chemicals. Here, we address the evolution of retinoic acid (RA) signalling in the Priapulida worm,
MeSH term(s)	Animals ; Aquatic Organisms/genetics ; Evolution, Molecular ; Phylogeny ; Receptors, Retinoic Acid/genetics ; Sequence Analysis, DNA/methods ; Signal Transduction
Chemical Substances	Receptors, Retinoic Acid
Language	English
Publishing date	2019-11-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes10120985
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Article ; Online: Discovery of contaminants with antagonistic activity against retinoic acid receptor in house dust.

Jia, Yingting / Zhang, Hong / Hu, Wenxin / Wang, Lei / Kang, Qiyue / Liu, Jiaying / Nakanishi, Tsuyoshi / Hiromori, Youhei / Kimura, Tomoki / Tao, Shu / Hu, Jianying

Journal of hazardous materials

2021 Volume 426, Page(s) 127847

Abstract	Retinoic acid receptors (RARs) control reproduction and development in vertebrates, but little attention has been paid to anthropogenic chemicals exhibiting RAR agoniztic/antagonistic activity. Here we applied a His-RARα pull-down assay combined with high-resolution mass spectrometry to identify chemicals with RARα activity in house dust. After screening, a total of 540 peaks were retained as potential RARα ligands. The mass spectra of 14 chemicals matched with those in the database, of which triphenyl phosphate, galaxolidone, di(2-ethylhexyl) phthalate (DEHP), tris(2-ethylhexyl) phosphate (TEHP), and tris(2-butoxyethyl) phosphate were confirmed by their standards. While one chemical in the sample matched with monophenyl phosphate in the MS/MS database, its retention time was much higher than that of monophenyl phosphate standard, suggesting that it may be an in-source fragment. Its parent ion was finally identified to be m/z 399.2663 using a similarity analysis among chromatographic peaks of hundreds of ions at the same retention time in MS
MeSH term(s)	Animals ; Dust ; Organophosphates/analysis ; Phosphates ; Receptors, Retinoic Acid ; Tandem Mass Spectrometry
Chemical Substances	Dust ; Organophosphates ; Phosphates ; Receptors, Retinoic Acid
Language	English
Publishing date	2021-11-20
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1491302-1
ISSN	1873-3336 ; 0304-3894
ISSN (online)	1873-3336
ISSN	0304-3894
DOI	10.1016/j.jhazmat.2021.127847
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