Expression of cytochrome P450 regulators in cynomolgus macaque

Abstract

1. Cytochrome P450 (P450) regulators including nuclear receptors and transcription factors have not been fully investigated in cynomolgus macaques, an important species used in drug metabolism studies. In this study, we analyzed 17 P450 regulators by sequence and phylogenetic analysis, and tissue expression.

2. Gene and genome structures of 17 P450 regulators were similar to the human orthologs, and the deduced amino acid sequences showed high sequence identities (92–95%) and more closely clustered in a phylogenetic tree, with the human orthologs.

3. Many of the P450 regulator mRNAs were preferentially expressed in the liver, kidney, and/or jejunum. Among the P450 regulator mRNAs, PXR was most abundant in the liver and jejunum, and HNF4α in the kidney. In the liver, the expression of most P450 regulator mRNAs did not show significant differential expression (>2.5-fold) between cynomolgus macaques bred in Cambodia, China, and Indonesia, or rhesus macaques.

4. By correlation analysis, most of the P450 regulators were significantly (p < 0.05) correlated to other P450 regulators, and many of them were also significantly (p < 0.05) correlated with P450s.

5. These results suggest that 17 P450 regulators of cynomolgus macaques had similar molecular characteristics to the human orthologs.

Keywords:

• Cynomolgus monkey
• cytochrome P450
• drug metabolism
• nuclear receptor
• transcription factor

Acknowledgments

Authors greatly thank Mr. Lance Bell for his advice on English writing.

Declaration of interest

The authors are responsible for the content and writing of the article and report no declarations of interest.