ToxSci Advance Access originally published online on May 5, 2006
Toxicological Sciences 2006 92(2):394-408; doi:10.1093/toxsci/kfl001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Cytochrome P450 1A4 and 1A5 in Common Cormorant (Phalacrocorax carbo): Evolutionary Relationships and Functional Implications Associated with Dioxin and Related Compounds
* Center for Marine Environmental Studies, Ehime University, Matsuyama 790-8577, Japan; Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, Marine Biological Laboratory, Woods Hole, Massachusetts 02543; and Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts 02543, USA
Received March 7, 2006; accepted April 21, 2006
The present study characterized cytochrome P4501A (CYP1A) isoforms from common cormorant (Phalacrocorax carbo) with regard to their evolutionary relationships and their roles in disposition of dioxin and related compounds (DRCs). Two clones isolated from a cormorant liver cDNA library were named CYP1A4 and CYP1A5 on the basis of greatest overall amino acid identity shared with chicken (Gallus gallus) CYP1A4 (78%) and CYP1A5 (78%), respectively. Spatial heterogeneity in phylogenetic signal along the sequences strongly indicated that cormorant CYP1A4 and CYP1A5 have undergone partial interparalog gene conversion, similar to chicken and mammalian CYP1As. Phylogenetic analysis of a putatively unconverted region produced a tree topology consistent with the orthology of avian CYP1A5s with mammalian CYP1A2s and avian CYP1A4s with mammalian CYP1A1s. Hepatic CYP1A4 and CYP1A5 mRNA levels in wild cormorants from Lake Biwa, Japan, were quantified to examine the effects of DRCs on isoform-specific expression and to evaluate the toxicokinetics of DRCs in which CYP1A expression is involved. Both CYP1A4 and CYP1A5 mRNA levels were positively correlated with total tetrachlorodibenzo-p-dioxin toxic equivalents and concentrations of each congener in most cases in the liver, suggesting the induction of both enzymes through a shared transcriptional mechanism. The lack of correlation of 2,3,7,8-tetrachlorodibenzofuran and 3,3',4,4'-tetrachlorobiphenyl (PCB77) to CYP1A gene expression is likely due to the rapid metabolism of these two congeners. Liver-to-muscle concentration ratios for most DRC congeners except PCB77 and mono-ortho coplanar polychlorinated biphenyls significantly increased with an elevation of CYP1A4 and CYP1A5 mRNA levels. The present data suggest that hepatic sequestration of some DRCs occurs in cormorant via binding to either CYP1A5 or both CYP1A4 and CYP1A5.
Key Words: CYP1A4; CYP1A5; gene conversion; dioxin and related compounds; metabolism; hepatic sequestration.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. Yasui, E.-Y. Kim, H. Iwata, D. G. Franks, S. I. Karchner, M. E. Hahn, and S. Tanabe Functional Characterization and Evolutionary History of Two Aryl Hydrocarbon Receptor Isoforms (AhR1 and AhR2) from Avian Species Toxicol. Sci., September 1, 2007; 99(1): 101 - 117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hirakawa, H. Iwata, Y. Takeshita, E.-Y. Kim, T. Sakamoto, Y. Okajima, M. Amano, N. Miyazaki, E. A. Petrov, and S. Tanabe Molecular Characterization of Cytochrome P450 1A1, 1A2, and 1B1, and Effects of Polychlorinated Dibenzo-p-dioxin, Dibenzofuran, and Biphenyl Congeners on Their Hepatic Expression in Baikal Seal (Pusa sibirica) Toxicol. Sci., June 1, 2007; 97(2): 318 - 335. [Abstract] [Full Text] [PDF]
|
|