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Sökning: id:"swepub:oai:DiVA.org:umu-21142" > Competitive Binding...

  • Weiss, Jana M (författare)

Competitive Binding of Poly- and Perfluorinated Compounds to the Thyroid Hormone Transport Protein Transthyretin

  • Artikel/kapitelEngelska2009

Förlag, utgivningsår, omfång ...

  • 2009-03-17
  • Oxford University Press of the Society of Toxicology,2009
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:umu-21142
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-21142URI
  • https://doi.org/10.1093/toxsci/kfp055DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Due to their unique surfactant properties, poly- and perfluorinated compounds (PFCs) have been extensively used, and can be found all over the environment.. Concern about their environmental fate and toxicological properties have initiated several research projects. In the present study, we investigated if PFCs can compete with thyroxin (T4, i.e. the transport form of thyroid hormone) for binding to the human thyroid hormone transport protein transthyretin (TTR). Such competitive capacity may lead to decreased thyroid hormone levels as previously reported for animals exposed to PFCs. Twenty four PFCs, together with six structurally similar natural fatty acids, were tested for binding capacity in a radioligand binding assay. The binding potency decreased in the order: PFHxS>PFOS/PFOA>PFHpA>L-PFOSi>PFNA, with TTR binding potencies 12.5-50 times lower than the natural ligand thyroxine (T4). Some lower molecular weight compounds with structural similarity to these PFCs were >100 times less potent than T4. Simple descriptors based on the two dimensional molecular structures of the compounds were used to visualize the chemical variation and to model the structure-activity relationship for the competitive potencies of the TTR-binding compounds. The models indicated the dependence on molecular size and functional group(s), but demanded a more detailed description of the chemical properties and data for validation and further QSAR development. Competitive binding of PFCs to TTR as observed for human TTR in the present study, may explain altered thyroid hormone levels described for PFC-exposed rats and monkeys. Median human blood levels of the most potent TTR-binding PFCs are 1-2 orders of magnitude lower than IC50-values determined in the present study. In addition, this study contributes to the understanding of the bioaccumulation of PFCs in man and possibly in other wildlife species.

Ämnesord och genrebeteckningar

  • Perfluorinated Compounds (PFCs)
  • Thyroid hormone
  • Thyroxine (T4)
  • Transthyretin (TTR) binding
  • Perfluorooctane sulfonate (PFOS)
  • Endocrine disruption

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Andersson, Patrik LUmeå universitet,Kemiska institutionen(Swepub:umu)paan0001 (författare)
  • Lamoree, Marja H (författare)
  • Leonards, Pim E G (författare)
  • van Leeuwen, Stefan P J (författare)
  • Hamers, Timo (författare)
  • Umeå universitetKemiska institutionen (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Toxicological sciences : an official journal of the Society of Toxicology: Oxford University Press of the Society of Toxicology109:2, s. 206-161096-0929
  • Ingår i:Toxicological Sciences: Oxford University Press of the Society of Toxicology109:2, s. 206-161096-6080

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