Cloning of rat cytochrome P450RAI (CYP26) cDNA and regulation of its gene expression by all-trans-retinoic acid in vivo

Y. Wang, R. Zolfaghari, Ross A. Catharine

Research output: Contribution to journalArticle

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Abstract

A novel retinoic acid (RA)-inducible cytochrome P450 (P450 RAI or CYP26), previously cloned from human, zebra fish, and mouse, functions in the metabolism of all-trans-RA to polar metabolites including 4-hydroxy-RA and 4-oxo-RA. To further study CYP26 in the rat model, we first cloned rat CYP26 cDNA. The nucleotide sequence predicts a 497-amino-acid protein whose sequence is 95% identical to mouse and 91% homologous to human CYP26. Animal studies showed that CYP26 mRNA expression is very low (0.01 ± 0.008; P < 0.05) in vitamin-A-deficient rats compared to pair-fed vitamin-A-sufficient rats (defined as 1.0). In a kinetic study, vitamin-A-deficient rats were treated with ∼ 100 μg of all-trans-RA and liver was collected after 3-72 h for analysis of CYP26 mRNA by quantitative real-time PCR. Liver CYP26 mRNA increased to nearly 10-fold above control after 3 h (P < 0.01), reaching a peak of about 2000-fold greater around 10 h (P < 0.001) and then decreased rapidly. The CYP26 dose response to RA was nearly linear (R2 = 0.9638). Additionally, significant regulation of CYP26 gene expression was observed in the vitamin-A-deficient, control, and RA-treated condition in lung, testis, and small intestine. We conclude that CYP26 mRNA expression is dynamically regulated in vivo by diet and RA in hepatic and extrahepatic tissues. The long-term down-regulation of CYP26 in retinoid deficiency may be critical for conserving RA, while the acute up-regulation of CYP26 may be important for preventing a deleterious overshoot of RA derived from either dietary or exogenous sources.

Original languageEnglish (US)
Pages (from-to)235-243
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume401
Issue number2
DOIs
StatePublished - May 15 2002

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

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