Limits...
Identification and analysis of CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 in cynomolgus macaques.

Uno Y, Hosaka S, Yamazaki H - J. Vet. Med. Sci. (2014)

Bottom Line: By phylogenetic analysis, each cynomolgus P450 was more closely related to the human ortholog as compared with the dog or rat ortholog.Tissue expression patterns of each cynomolgus P450 were generally similar to that of the human ortholog.These results suggest the molecular similarities of CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 between cynomolgus macaques and humans.

View Article: PubMed Central - PubMed

Affiliation: Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd., Kainan, Wakayama 642-0017, Japan.

ABSTRACT
Cytochromes P450 (P450) are important for not only drug metabolism and toxicity, but also biosynthesis and metabolism of cholesterol and bile acids, and steroid synthesis. In cynomolgus macaques, widely used in biomedical research, we have characterized P450 cDNAs, which were isolated as expressed sequence tags of cynomolgus macaque liver. In this study, cynomolgus CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 cDNAs were characterized by sequence analysis, phylogenetic analysis and tissue expression pattern. By sequence analysis, these five cynomolgus P450s had high sequence identities (94-99%) to the human orthologs in amino acids. By phylogenetic analysis, each cynomolgus P450 was more closely related to the human ortholog as compared with the dog or rat ortholog. By quantitative polymerase chain reaction, among the 10 tissue types, CYP7A1 and CYP17A1 mRNAs were preferentially expressed in liver and adrenal gland, respectively. Cynomolgus CYP27A1 and CYP51A1 mRNAs were most abundantly expressed in liver and testis, respectively. Cynomolgus CYP20A1 mRNA was expressed in all the tissues, including brain and liver. Tissue expression patterns of each cynomolgus P450 were generally similar to that of the human ortholog. These results suggest the molecular similarities of CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 between cynomolgus macaques and humans.

Show MeSH

Related in: MedlinePlus

Phylogeny of cynomolgus P450s. A phylogenetic tree was created using the neighborjoining method. CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 amino acid sequences werefrom humans (h), cynomolgus macaques (mf), dogs (d) and rats (r). Human CYP39A1 was usedas outgroup. For the distance measurement, the scale bar indicates 0.1 amino acidsubstitutions per site.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4300383&req=5

fig_001: Phylogeny of cynomolgus P450s. A phylogenetic tree was created using the neighborjoining method. CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 amino acid sequences werefrom humans (h), cynomolgus macaques (mf), dogs (d) and rats (r). Human CYP39A1 was usedas outgroup. For the distance measurement, the scale bar indicates 0.1 amino acidsubstitutions per site.

Mentions: Cynomolgus CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 had the sequence structurescharacteristic of P450 enzymes, including the heme-binding region. The exception was that theheme-binding region of cynomolgus CYP20A1 could not be determined due to an incomplete ORF asdescribed earlier. Phylogenetic analysis was performed using CYP7A1, CYP17A1, CYP20A1, CYP27A1and CYP51A1 amino acid sequences of humans, cynomolgus macaques, dogs and rats. The resultindicated that cynomolgus CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 were more closelyclustered with the human ortholog as compared with the dog or rat ortholog (Fig. 1Fig. 1.


Identification and analysis of CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 in cynomolgus macaques.

Uno Y, Hosaka S, Yamazaki H - J. Vet. Med. Sci. (2014)

Phylogeny of cynomolgus P450s. A phylogenetic tree was created using the neighborjoining method. CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 amino acid sequences werefrom humans (h), cynomolgus macaques (mf), dogs (d) and rats (r). Human CYP39A1 was usedas outgroup. For the distance measurement, the scale bar indicates 0.1 amino acidsubstitutions per site.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4300383&req=5

fig_001: Phylogeny of cynomolgus P450s. A phylogenetic tree was created using the neighborjoining method. CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 amino acid sequences werefrom humans (h), cynomolgus macaques (mf), dogs (d) and rats (r). Human CYP39A1 was usedas outgroup. For the distance measurement, the scale bar indicates 0.1 amino acidsubstitutions per site.
Mentions: Cynomolgus CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 had the sequence structurescharacteristic of P450 enzymes, including the heme-binding region. The exception was that theheme-binding region of cynomolgus CYP20A1 could not be determined due to an incomplete ORF asdescribed earlier. Phylogenetic analysis was performed using CYP7A1, CYP17A1, CYP20A1, CYP27A1and CYP51A1 amino acid sequences of humans, cynomolgus macaques, dogs and rats. The resultindicated that cynomolgus CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 were more closelyclustered with the human ortholog as compared with the dog or rat ortholog (Fig. 1Fig. 1.

Bottom Line: By phylogenetic analysis, each cynomolgus P450 was more closely related to the human ortholog as compared with the dog or rat ortholog.Tissue expression patterns of each cynomolgus P450 were generally similar to that of the human ortholog.These results suggest the molecular similarities of CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 between cynomolgus macaques and humans.

View Article: PubMed Central - PubMed

Affiliation: Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd., Kainan, Wakayama 642-0017, Japan.

ABSTRACT
Cytochromes P450 (P450) are important for not only drug metabolism and toxicity, but also biosynthesis and metabolism of cholesterol and bile acids, and steroid synthesis. In cynomolgus macaques, widely used in biomedical research, we have characterized P450 cDNAs, which were isolated as expressed sequence tags of cynomolgus macaque liver. In this study, cynomolgus CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 cDNAs were characterized by sequence analysis, phylogenetic analysis and tissue expression pattern. By sequence analysis, these five cynomolgus P450s had high sequence identities (94-99%) to the human orthologs in amino acids. By phylogenetic analysis, each cynomolgus P450 was more closely related to the human ortholog as compared with the dog or rat ortholog. By quantitative polymerase chain reaction, among the 10 tissue types, CYP7A1 and CYP17A1 mRNAs were preferentially expressed in liver and adrenal gland, respectively. Cynomolgus CYP27A1 and CYP51A1 mRNAs were most abundantly expressed in liver and testis, respectively. Cynomolgus CYP20A1 mRNA was expressed in all the tissues, including brain and liver. Tissue expression patterns of each cynomolgus P450 were generally similar to that of the human ortholog. These results suggest the molecular similarities of CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 between cynomolgus macaques and humans.

Show MeSH
Related in: MedlinePlus