Document Detail

Constitutive androstane receptor (CAR) as a potential sensing biomarker of persistent organic pollutants (POPs) in aquatic mammal: molecular characterization, expression level, and ligand profiling in Baikal seal (Pusa sibirica).
MedLine Citation:
PMID:  16929008     Owner:  NLM     Status:  MEDLINE    
To characterize the function of constitutive active/androstane receptor (CAR) in aquatic mammals, CAR complementary DNA (cDNA) was cloned from the liver of Baikal seal (Pusa sibirica) from Lake Baikal, Russia, and the messenger RNA (mRNA) expression levels in various tissues/organs of the wild population and the CAR ligand profiles were investigated. The seal CAR cDNA had an open reading frame of 1047 bp encoding 348 amino acids that revealed 74-84% amino acid identities with CARs from rodents and human. The mRNA expression profile of tissues/organs represented that Baikal seal CAR was predominantly expressed in the liver followed by heart and intestine. The expression analysis of hepatic CAR mRNA showed no correlation with expression of cytochrome P450 (CYP) 1A, 1B, 2B, 2C, and 3A-like proteins, indicating that the CAR expression level may not be the sole determinant of the regulation of these CYP expressions in the seal liver. There was no significant correlation between CAR expression and any of the persistent organic pollutants (POPs) levels. Furthermore, we performed an in vitro CAR transactivation assay using MCF-7 cells transfected with Baikal seal CAR expression plasmid and (NR1)(3)-luciferase reporter gene plasmid. In the transactivation analysis of Baikal seal CAR, neither repression by androstanol and androstenol, nor activation by estrone and estradiol, which are recognized as endogenous ligands for mouse and human CARs, was detected. On the other hand, bile acids such as chenodeoxycholic acid, deoxycholic acid, and lithocholic acid activated the seal CAR as well as mouse CAR. As for exogenous chemicals, the seal CAR was transactivated by a human CAR agonist, 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime), but not by a mouse CAR agonist, (1,4-bis[2-(3,5-dichloropyridyloxy)]benzene). In addition, the seal CAR was also activated by polychlorinated biphenyls (PCBs) (Kanechlor-500, International Union of Pure and Applied Chemistry No. PCB153; 2,2',4,4',5,5'-hexachlorobiphenyl and PCB180; 2,2',3,4,4',5,5'-heptachlorobiphenyl), and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) and its metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE). The seal CAR responded more sensitively to PCBs than the mouse CAR. Based on the results of CAR transactivation assay, the lowest observable effect levels of Kanechlor-500, PCB153, PCB180, p,p'-DDT, and p,p'-DDE in Baikal seal were estimated to be 10, 20, 20, 10, and 10 ppm on wet weight basis, respectively. These results suggest that CAR is conserved in diverse mammalian species including seals. Whereas the seal CAR-mediated gene transcription may potentially be a sensitive response to the exposure of certain POPs, the ligand profile of seal CAR may be different from those of other mammalian CARs. This study indicates that CAR-mediated responses may be useful information to assess the ecotoxicological risk of xenobiotics such as POPs in wildlife but the previous results derived from rodent and human CAR may not be applicable to the risk assessment in wild species.
Hiroki Sakai; Hisato Iwata; Eun-Young Kim; Oyuna Tsydenova; Nobuyuki Miyazaki; Evgeny A Petrov; Valeriy B Batoev; Shinsuke Tanabe
Related Documents :
9778148 - Induction of dna fragmentation and hsp72 immunoreactivity by adenovirus-mediated gene t...
9414258 - A recombinant e1-deleted canine adenoviral vector capable of transduction and expressio...
16352528 - Regulatable gutless adenovirus vectors sustain inducible transgene expression in the br...
9188608 - High level of transgene expression in cell cultures and in the mouse by replication-inc...
22965118 - Solitary restriction endonucleases in prokaryotic genomes.
16633348 - Endogenous microrna regulation suppresses transgene expression in hematopoietic lineage...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-08-23
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  94     ISSN:  1096-6080     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-10-05     Completed Date:  2007-03-13     Revised Date:  2010-09-17    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  57-70     Citation Subset:  IM    
Center for Marine Environmental Studies (CMES), Ehime University, Matsuyama 790-8577, Japan.
Data Bank Information
Bank Name/Acc. No.:
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Amino Acid Sequence
Biological Markers / analysis,  metabolism
Cell Line, Tumor
Cloning, Molecular
DDT / pharmacology
DNA, Complementary / chemistry,  genetics,  isolation & purification
Dichlorodiphenyl Dichloroethylene / pharmacology
Gene Expression Profiling
Luciferases / genetics,  metabolism
Molecular Sequence Data
Phoca / genetics*,  metabolism
Polychlorinated Biphenyls / pharmacology
RNA, Messenger / genetics,  metabolism
Receptors, Cytoplasmic and Nuclear / agonists,  genetics*,  metabolism
Recombinant Fusion Proteins / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis, DNA
Sequence Homology, Amino Acid
Transcription Factors / agonists,  genetics*,  metabolism
Transcription, Genetic / drug effects
Water Pollutants, Chemical / analysis*,  isolation & purification,  pharmacology
Reg. No./Substance:
0/Biological Markers; 0/DNA, Complementary; 0/Ligands; 0/Polychlorinated Biphenyls; 0/RNA, Messenger; 0/Receptors, Cytoplasmic and Nuclear; 0/Recombinant Fusion Proteins; 0/Transcription Factors; 0/Water Pollutants, Chemical; 0/constitutive androstane receptor; 50-29-3/DDT; 72-55-9/Dichlorodiphenyl Dichloroethylene; EC 1.13.12.-/Luciferases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  The spontaneously hypertensive rat: an experimental model of sulfur dioxide-induced airways disease.
Next Document:  In utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin induces amphiregulin gene expression in the...