SwePub
Sök i LIBRIS databas

  Utökad sökning

id:"swepub:oai:DiVA.org:umu-21142"
 

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

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003767naa a2200421 4500
001oai:DiVA.org:umu-21142
003SwePub
008090403s2009 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-211422 URI
0247 a https://doi.org/10.1093/toxsci/kfp0552 DOI
040 a (SwePub)umu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Weiss, Jana M4 aut
2451 0a Competitive Binding of Poly- and Perfluorinated Compounds to the Thyroid Hormone Transport Protein Transthyretin
264 c 2009-03-17
264 1b Oxford University Press of the Society of Toxicology,c 2009
338 a print2 rdacarrier
520 a 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.
653 a Perfluorinated Compounds (PFCs)
653 a Thyroid hormone
653 a Thyroxine (T4)
653 a Transthyretin (TTR) binding
653 a Perfluorooctane sulfonate (PFOS)
653 a Endocrine disruption
7001 a Andersson, Patrik Lu Umeå universitet,Kemiska institutionen4 aut0 (Swepub:umu)paan0001
7001 a Lamoree, Marja H4 aut
7001 a Leonards, Pim E G4 aut
7001 a van Leeuwen, Stefan P J4 aut
7001 a Hamers, Timo4 aut
7102 a Umeå universitetb Kemiska institutionen4 org
7730 t Toxicological sciences : an official journal of the Society of Toxicologyd : Oxford University Press of the Society of Toxicologyg 109:2, s. 206-16q 109:2<206-16x 1096-0929
7730 t Toxicological Sciencesd : Oxford University Press of the Society of Toxicologyg 109:2, s. 206-16q 109:2<206-16x 1096-6080
8564 u https://academic.oup.com/toxsci/article-pdf/109/2/206/16679833/kfp055.pdf
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-21142
8564 8u https://doi.org/10.1093/toxsci/kfp055

Hitta via bibliotek

Till lärosätets databas

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy