Linked Life Data

21163906

Source:http://linkedlifedata.com/resource/pubmed/id/21163906

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-2-24
pubmed:abstractText
The objectives of this study were to determine the structural characteristics of perfluoroalkyl acids (PFAAs) that confer estrogen-like activity in vivo using juvenile rainbow trout (Oncorhynchus mykiss) as an animal model and to determine whether these chemicals interact directly with the estrogen receptor (ER) using in vitro and in silico species comparison approaches. Perfluorooctanoic (PFOA), perfluorononanoic (PFNA), perfluorodecanoic (PFDA), and perfluoroundecanoic (PFUnDA) acids were all potent inducers of the estrogen-responsive biomarker protein vitellogenin (Vtg) in vivo, although at fairly high dietary exposures. A structure-activity relationship for PFAAs was observed, where eight to ten fluorinated carbons and a carboxylic acid end group were optimal for maximal Vtg induction. These in vivo findings were corroborated by in vitro mechanistic assays for trout and human ER. All PFAAs tested weakly bound to trout liver ER with half maximal inhibitory concentration (IC(50)) values of 15.2-289 ?M. Additionally, PFOA, PFNA, PFDA, PFUnDA, and perlfuorooctane sulfonate (PFOS) significantly enhanced human ER?-dependent transcriptional activation at concentrations ranging from 10-1000 nM. Finally, we employed an in silico computational model based upon the crystal structure for the human ER? ligand-binding domain complexed with E2 to structurally investigate binding of these putative ligands to human, mouse, and trout ER?. PFOA, PFNA, PFDA, and PFOS all efficiently docked with ER? from different species and formed a hydrogen bond at residue Arg394/398/407 (human/mouse/trout) in a manner similar to the environmental estrogens bisphenol A and nonylphenol. Overall, these data support the contention that several PFAAs are weak environmental xenoestrogens of potential concern.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1096-0929
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
120
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
42-58
pubmed:meshHeading
pubmed-meshheading:21163906-Acids, Acyclic, pubmed-meshheading:21163906-Animals, pubmed-meshheading:21163906-Binding, Competitive, pubmed-meshheading:21163906-Biological Markers, pubmed-meshheading:21163906-Dose-Response Relationship, Drug, pubmed-meshheading:21163906-Environmental Pollutants, pubmed-meshheading:21163906-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:21163906-Estrogen Receptor alpha, pubmed-meshheading:21163906-Estrogens, Non-Steroidal, pubmed-meshheading:21163906-Fluorocarbons, pubmed-meshheading:21163906-Humans, pubmed-meshheading:21163906-Liver, pubmed-meshheading:21163906-Molecular Structure, pubmed-meshheading:21163906-Oncorhynchus mykiss, pubmed-meshheading:21163906-Protein Binding, pubmed-meshheading:21163906-Receptors, Estrogen, pubmed-meshheading:21163906-Species Specificity, pubmed-meshheading:21163906-Structure-Activity Relationship, pubmed-meshheading:21163906-Vitellogenins
pubmed:year
2011
pubmed:articleTitle
Estrogen-like activity of perfluoroalkyl acids in vivo and interaction with human and rainbow trout estrogen receptors in vitro.
pubmed:affiliation
Department of Animal, Dairy, and Veterinary Sciences and Graduate Program in Toxicology, Utah State University, 4815 Old Main Hill, Logan, Utah 84322-4815, USA. abby.benninghoff@usu.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural