Development and Characterization of a Human Reporter Cell Line for the Assessment of Thyroid Receptor Transcriptional Activity: A Case of Organotin Endocrine Disruptors
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26208032
DOI
10.1021/acs.jafc.5b01519
Knihovny.cz E-zdroje
- Klíčová slova
- cell line, luciferase reporter assay, organic tin compounds, thyroid hormone, thyroid receptor,
- MeSH
- aktivace transkripce účinky léků MeSH
- buněčné linie účinky léků metabolismus MeSH
- endokrinní disruptory farmakologie MeSH
- lidé MeSH
- promotorové oblasti (genetika) účinky léků MeSH
- receptory thyreoidních hormonů genetika metabolismus MeSH
- reportérové geny účinky léků MeSH
- transfekce MeSH
- trijodthyronin metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- endokrinní disruptory MeSH
- receptory thyreoidních hormonů MeSH
- trijodthyronin MeSH
We developed and characterized the human luciferase reporter cell line PZ-TR for the assessment of thyroid receptor (TR) transcriptional activity. Triiodothyronine (T3) induced luciferase activity in a dose-dependent manner, and the sensitivity of assay allowed for the detection of nanomolar T3 concentrations. The luciferase activity was induced by a maximum of (2.42 ± 0.14)-(2.73 ± 0.23)-fold after 24 h of exposure to 10 nM T3. We did not observe a nonspecific induction of luciferase activity by other steroid hormones and VDR ligands, with the exception of partial activation by retinoic acids. Cryopreservation of PZ-TR cells did not influence their functionality, responsivity to T3, or cell morphology, even after long-term cultivation. PZ-TR cells were used to evaluate the effects of organic tin compounds on TR. We found that the tributyltin and triphenyltin derivatives induced luciferase activity and that application of organotins in combination with T3 enhanced the effect of T3. These findings indicate that organic tin compounds have potential to interfere with TR-mediated regulation of gene expression and influence the physiological activity of thyroid hormones.
Citace poskytuje Crossref.org
Targeting the pregnane X receptor using microbial metabolite mimicry