Aryl hydrocarbon receptor knockout mice (AHR(-/-)) exhibit liver retinoid accumulation and reduced retinoic acid metabolism

Fausto Andreola, Pedro M. Fernandez-Salguero, Maria V. Chiantore, Martin P. Petkovich, Frank J. Gonzalez, Luigi M. De Luca

Research output: Contribution to journalArticle

Abstract

Livers from aryl hydrocarbon receptor-null mice showed a 3-fold increase in retinoids and a 65% decrease in retinoic acid metabolism. Levels of expression of the retinoic acid 4-hydroxylase, P450RAI, did not change, whereas cytochrome P4501A2 levels were lower in the null mouse, as shown earlier; however, this enzyme was found not to be active toward retinoic acid. These data suggest that aryl hydrocarbon receptor controls retinoic acid catabolism, through modulation of an unidentified target gene. Aldehyde dehydrogenases 1 and 2 were down-regulated markedly in the aryl hydrocarbon receptor-deficient mouse liver. 2,3,7,8-Tetrachlorodibenzo-p-dioxin induced cytochrome P4501A2 but not the aldehyde dehydrogenases in wild-type mice, suggesting that aryl hydrocarbon receptor is not involved directly in the down-regulation of this gene. Transglutaminase II, a retinoic acid-responsive gene product, was increased 2-fold, consistent with the liver fibrosis phenotype observed in the null mice. These findings suggest a molecular connection between xenobiotic-activated receptor signaling and retinoid homeostasis.

Original languageEnglish (US)
Pages (from-to)2835-2838
Number of pages4
JournalCancer Research
Volume57
Issue number14
StatePublished - Jul 15 1997

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Andreola, F., Fernandez-Salguero, P. M., Chiantore, M. V., Petkovich, M. P., Gonzalez, F. J., & De Luca, L. M. (1997). Aryl hydrocarbon receptor knockout mice (AHR(-/-)) exhibit liver retinoid accumulation and reduced retinoic acid metabolism. Cancer Research, 57(14), 2835-2838.