Disruption of thyroid hormone binding to sea bream recombinant transthyretin by ioxinyl and polybrominated diphenyl ethers

Morgado, Isabel; Hamers, Timo; Ven, Leo van der; Power, Deborah M.

doi:10.1016/j.chemosphere.2007.04.010

Cited by 81 publications

(40 citation statements)

References 47 publications

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“…Tetrabromobisphenol A and pentabromophenol were the most potent chemicals in halogenated phenolic compounds with two phenolic rings and with a single ring, respectively. The structural preference of ligand binding was well conserved in vertebrate evolution (Kudo et al, 2006;Meerts et al, 2000;Morgado et al, 2007;Yamauchi et al, 2003). Furthermore, in the structureactivity relationships, halogen species-dependency (Br À > Cl À in pentahalogenated phenols; I À > Br À % Cl À in trihalogented phenols; Br À > Cl À > no halogen in bisphenol A) and halogen numberdependency (penta-> tri-in brominated and chlorinated phenols) are similar with previous studies using human (Meerts et al, 2000), chicken and amphibian TTRs (Kudo et al, 2006;Yamauchi et al, 2003).…”

Section: Discussionsupporting

confidence: 80%

Characterization of little skate (Leucoraja erinacea) recombinant transthyretin: Zinc-dependent 3,3′,5-triiodo-l-thyronine binding

Suzuki

Kasai

Yamauchi

2015

General and Comparative Endocrinology

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Transthyretin (TTR) diverged from an ancestral 5-hydroxyisourate hydrolase (HIUHase) by gene duplication at some early stage of chordate evolution. To clarify how TTR had participated in the thyroid system as an extracellular thyroid hormone (TH) binding protein, TH binding properties of recombinant little skate Leucoraja erinacea TTR was investigated. At the amino acid level, skate TTR showed 37-46% identities with the other vertebrate TTRs. Because the skate TTR had a unique histidine-rich segment in the N-terminal region, it could be purified by Ni-affinity chromatography. The skate TTR was a 46-kDa homotetramer of 14.5kDa subunits, and had one order of magnitude higher affinity for 3,3',5-triiodo-l-thyronine (T3) and some halogenated phenols than for l-thyroxine. However, the skate TTR had no HIUHase activity. Ethylenediaminetetraacetic acid (EDTA) treatment inhibited [(125)I]T3 binding activity whereas the addition of Zn(2+) to the EDTA-treated TTR recovered [(125)I]T3 binding activity in a Zn(2+) concentration-dependent manner. Scatchard analysis revealed the presence of two classes of binding site for T3, with dissociation constants of 0.24 and 17nM. However, the high-affinity sites were completely abolished with 1mM EDTA, whereas the remaining low-affinity sites decreased binding capacity. The number of zinc per TTR was quantified to be 4.5-6.3. Our results suggest that skate TTR has tight Zn(2+)-binding sites, which are essential for T3 binding to at least the high-affinity sites. Zn(2+) binding to the N-terminal histidine-rich segment may play an important role in acquisition or reinforcement of TH binding ability during early evolution of TTR.

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Section: Discussionsupporting

confidence: 80%

Characterization of little skate (Leucoraja erinacea) recombinant transthyretin: Zinc-dependent 3,3′,5-triiodo-l-thyronine binding

Suzuki

Kasai

Yamauchi

2015

General and Comparative Endocrinology

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“…A number of wide spread tetra-and pentabrominated BDEs and commercial PeBDE showed competitive binding to both human and fish transthyretin, a major plasma thyroid hormone binding protein, in vitro (Hamers et al, 2006;Morgado et al, 2007). Interactions with sex steroid receptors were also observed in vitro (Hamers et al, 2006).…”

Section: Introductionmentioning

confidence: 87%

Toxicity of analytically cleaned pentabromodiphenylether after prolonged exposure in estuarine European flounder (Platichthys flesus), and partial life-cycle exposure in fresh water zebrafish (Danio rerio)

Kuiper

Vethaak²,

Cantón

et al. 2008

Chemosphere

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a b s t r a c tResidues of polybrominated diphenylethers (PBDEs), extensively applied as flame retardants, are widely spread in the aquatic environment and biota. The present study investigates effects of the environmentally relevant lower brominated diphenylethers in two fish species in vivo under controlled laboratory conditions. Euryhaline flounder (Platichthys flesus) and freshwater zebrafish (Danio rerio) were exposed to a range of concentrations of a commercial pentabromodiphenylether mixture, DE-71. Chemical analysis of exposed fish showed a pattern of PBDE congeners that was very similar to that in wild fish. The resulting range included environmentally relevant, as well as higher levels. Animals were investigated histopathologically with emphasis on endocrine and reproductive organs. In zebrafish, hatching of embryos and larval development were assessed. Biochemical parameters were investigated in flounder as markers for suggested dioxin-like activity (ethoxyresorufin-O-deethylase = EROD), and activation of endogenous estrogen synthesis (gonad aromatase activity). Thyroid hormones were analyzed in plasma in both species. Benchmark analysis using internal PBDE concentrations showed a mild dose-dependent decrease of hepatic EROD and ovarian aromatase activities, and plasma thyroxin levels in flounder, and an increase of plasma thyroid hormone levels in zebrafish. These trends did not result in statistically significant differences from control fish, and major histopathological changes were not observed. Reproduction in zebrafish appeared to be the most sensitive parameter with statistically significantly reduced larval survival and non-significant indications for decreased egg production at internal levels that were more than 55 times the highest environmental recordings. The present results indicate limited risk for endocrine or reproductive effects of current environmental PBDE contamination in fish.

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“…Several environmental contaminants interfere with TH homeostasis by binding TTR in vertebrates (Yamauchi et al, 2003;Morgado et al, 2007a). The TTR is mainly expressed in the liver and brain (choroid plexus) in mammalians (Murakami et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Changes of thyroid hormone levels and related gene expression in Chinese rare minnow (Gobiocypris rarus) during 3-amino-1,2,4-triazole exposure and recovery

Zha

Spear

et al. 2009

Aquatic Toxicology

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a b s t r a c tThyroid hormones (THs) play an important role in the development and metabolism of fish through their influences on genetic transcription and are targets for endocrine disruptive agents in the aquatic environment. Amitrole is a pesticide potentially interfering with thyroid hormone regulation. In this study, the rare minnow (Gobiocypris rarus) was exposed to different levels of 3-amino-1,2,4-triazole (amitrole) and allowed to recover in clean water. Plasma TH levels and the expression of TH-related genes, including transthyretin (ttr), deiodinases (d1 and d2), and the thyroid hormone receptor (tr˛) from the livers and brains were evaluated. After exposure, the plasma TH levels did not change. Histopathological observations showed that livers were degenerated at 10,000 ng/l and these damages could be recovered by the withdrawal of amitrole. However, the ttr, d1, and d2 mRNA levels in the livers of males were significantly up-regulated in all exposure groups (p < 0.05). The ttr and d2 mRNA levels were significantly up-regulated at 10,000 ng/l and 10, 100, and 1000 ng/l in the livers of females, respectively (p < 0.05). In the brains of males, a twofold increase of d2 mRNA levels at ≥100 ng/l and a fivefold decrease of tr˛mRNA levels at ≥10 ng/l were observed (p < 0.05), whereas no significant differences were observed in the expression of d2 and tr˛in the brains of females. After a recovery period, the ttr, d1, and d2 mRNA levels in the livers of males returned to control levels, but the tr˛mRNA levels were irreversibly decreased at all treatments (p < 0.05). In addition, the d2 mRNA levels in the livers of females were significantly induced at ≥100 ng/l. Moreover, the d2 mRNA levels in the brains of males and females were up-regulated at 10,000 ng/l. These results indicated that amitrole exposure could result in alternations of ttr, d1, d2, and tr˛gene expression in different tissues of the rare minnow. The expression of these TH-related genes in males was more sensitive to amitrole than those of females. Recovery in clean water was associated with the selective regulation of TH-related gene transcription in the rare minnow. Therefore, these TH-related genes can serve as biomarkers to screen the effects of thyroid disruption chemicals in rare minnow.

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Disruption of thyroid hormone binding to sea bream recombinant transthyretin by ioxinyl and polybrominated diphenyl ethers

Cited by 81 publications

References 47 publications

Characterization of little skate (Leucoraja erinacea) recombinant transthyretin: Zinc-dependent 3,3′,5-triiodo-l-thyronine binding

Characterization of little skate (Leucoraja erinacea) recombinant transthyretin: Zinc-dependent 3,3′,5-triiodo-l-thyronine binding

Toxicity of analytically cleaned pentabromodiphenylether after prolonged exposure in estuarine European flounder (Platichthys flesus), and partial life-cycle exposure in fresh water zebrafish (Danio rerio)

Changes of thyroid hormone levels and related gene expression in Chinese rare minnow (Gobiocypris rarus) during 3-amino-1,2,4-triazole exposure and recovery

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