Linked Life Data

18504957

Source:http://linkedlifedata.com/resource/pubmed/id/18504957

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2008-5-28
pubmed:abstractText
To investigate the biological effects of perfluorochemicals (PFCs) and to identify biomarkers of exposure to PFCs, this study focused on the effects mediated by peroxisome proliferator-activated receptor alpha (PPARalpha) in Baikal seals (Pusa sibirica). We cloned a full-length cDNA, encoding PPARalpha from the liver of Baikal seal, which has a deduced open reading frame of 468-amino acid residues with a predicted molecular mass of 52.2 kDa. Comparison of the amino-acid sequence of Baikal seal PPARalpha with that of other mammalian PPARalpha showed considerable similarities with PPARalpha of dog (97%), human (95%), rat (92%), and mouse (91%). The quantitative real-time RT-PCR analyses of tissues from Baikal seals revealed that PPARalpha mRNAs were primarily expressed in the liver, kidney, heart, and muscle. The hepatic expression levels of PPARalpha mRNA showed a positive correlation with the expression levels of immunochemically detected cytochrome P450 (CYP) 4A-like protein, indicating that the PPARalpha-CYP4A signaling pathway in Baikal seal is likely conserved. This study also developed an in vitro PPARalpha reporter gene assay using African green monkey kidney CV-1 cells transiently transfected with Baikal seal PPARalpha cDNA expression vector and a reporter vector containing a peroxisome proliferator-responsive element The in vitro reporter gene assay displayed significant response to clofibrate, which is a known PPARalpha agonist in humans and rodents. Treatmentwith perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), or perfluorooctane sulfonate (PFOS) induced PPARalpha-mediated transcriptional activity in a dose-dependent manner, showing the lowest-observed-effect concentrations of 62.5, 125, 125, 62.5, and 125 microM, respectively. In the livers of wild Baikal seals, expression levels of PPARalpha mRNA showed a significant positive correlation with PFNA levels. Moreover, expression of hepatic CYP4A-like protein was significantly correlated with the hepatic concentrations of PFNA and PFDA. These results suggest modulation of the PPARalpha-CYP4A signaling pathway by PFCs in the wild Baikal seals. Our study demonstrates that the PPARalpha-mediated response may be a useful biomarkerto evaluate potential biological effects of PFCs in wildlife.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0013-936X
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2302-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Contamination and effects of perfluorochemicals in Baikal seal (Pusa sibirica). 2. Molecular characterization, expression level, and transcriptional activation of peroxisome proliferator-activated receptor alpha.
pubmed:affiliation
Center for Marine Environmental Studies, Ehime University, Matsuyama 790-8577, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't