Disruption of thyroid hormone sulfotransferase activity by brominated flame retardant chemicals in the human choriocarcinoma placenta cell line, BeWo
Autor: | Christopher Leonetti, Craig M. Butt, Heather M. Stapleton |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Thyroid Hormones medicine.medical_specialty Sulfotransferase Environmental Engineering Halogenation Diiodothyronines Placenta Health Toxicology and Mutagenesis Polybrominated Biphenyls Thyroid Gland 010501 environmental sciences Hydroxylation 01 natural sciences Article 03 medical and health sciences Polybrominated diphenyl ethers Phenols Pregnancy Cell Line Tumor Internal medicine Halogenated Diphenyl Ethers medicine Humans Environmental Chemistry Choriocarcinoma Flame Retardants 0105 earth and related environmental sciences Fetus Chemistry Public Health Environmental and Occupational Health General Medicine General Chemistry medicine.disease Pollution 030104 developmental biology Endocrinology medicine.anatomical_structure Nuclear receptor Brominated flame retardant Female Sulfotransferases Protein Binding Hormone |
Zdroj: | Chemosphere. 197:81-88 |
ISSN: | 0045-6535 |
Popis: | Brominated flame retardants (BFRs) have been shown to disrupt thyroid hormone (TH) homeostasis through multiple mechanisms, including inhibition of enzymes that regulate intracellular levels of THs, such as sulfotransferases (SULTs). The placenta plays a critical role in helping to maintain TH levels during fetal development and expresses SULTs. This is concerning given that disruption of TH regulation within the placenta could potentially harm the developing fetus. In this study, we investigated the effects of two polybrominated diphenyl ethers (PBDEs), two hydroxylated PBDEs, and 2,4,6-tribromophenol (2,4,6-TBP) on TH SULT activity in a choriocarcinoma placenta cell line (BeWo). BeWo cells were exposed to BFR concentrations up to 1 μM for 1 – 24 h to investigate changes in basal SULT activity and in mRNA expression of several TH regulating genes. 2,4,6-TBP was the most potent inhibitor of basal 3,3′-T2 SULT activity at all exposure durations, decreasing activity by as much as 86% after 24 h of exposure. BDE-99, 3-OH BDE-47, and 6-OH BDE-47 also decreased 3,3′-T2 SULT activity by 23 – 42% at concentrations of 0.5 μM and 1.0 μM following 24 h exposures. BDE-47 had no effect on SULT activity, and there was no observed effect of any BFR exposure on expression of SULT1A1, or thyroid nuclear receptors alpha or beta. This research demonstrates that total TH SULT activity in placental cells are sensitive to BFR exposure; however, the mechanisms and consequences have yet to be fully elucidated. |
Databáze: | OpenAIRE |
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