Avian cytochrome P450 (CYP) 1-3 family genes: isoforms, evolutionary relationships, and mRNA expression in chicken liver

PLoS One. 2013 Sep 30;8(9):e75689. doi: 10.1371/journal.pone.0075689. eCollection 2013.

Abstract

Cytochrome P450 (CYP) of chicken and other avian species have been studied primarily with microsomes or characterized by cloning and protein expression. However, the overall existing isoforms in avian CYP1-3 families or dominant isoforms in avian xenobiotic metabolism have not yet been elucidated. In this study, we aimed to clarify and classify all of the existing isoforms of CYP1-3 in avian species using available genome assemblies for chicken, zebra finch, and turkey. Furthermore, we performed qRT-PCR assay to identify dominant CYP genes in chicken liver. Our results suggested that avian xenobiotic-metabolizing CYP genes have undergone unique evolution such as CYP2C and CYP3A genes, which have undergone avian-specific gene duplications. qRT-PCR experiments showed that CYP2C45 was the most highly expressed isoform in chicken liver, while CYP2C23b was the most highly induced gene by phenobarbital. Considering together with the result of further enzymatic characterization, CYP2C45 may have a dominant role in chicken xenobiotic metabolism due to the constitutive high expression levels, while CYP2C23a and CYP2C23b can be greatly induced by chicken xenobiotic receptor (CXR) activators. These findings will provide not only novel insights into avian xenobiotic metabolism, but also a basis for the further characterization of each CYP gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avian Proteins / metabolism*
  • Chickens / genetics*
  • Cytochrome P-450 Enzyme System / genetics*
  • Evolution, Molecular*
  • Liver / metabolism*
  • Phylogeny*
  • Protein Isoforms / genetics
  • RNA, Messenger / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Species Specificity
  • Synteny / genetics

Substances

  • Avian Proteins
  • CXR protein, chicken
  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Cytochrome P-450 Enzyme System

Grants and funding

This study was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT) awarded to Prof. M. Ishizuka (Nos. 24248056 and 24405004) and JSPS Fellowship for KPW (231864). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.