Identification of aldehyde oxidase 1 and aldehyde oxidase homologue 1 as dioxin-inducible genes

Steven P. Rivera, Hyun Ho Choi, Brett Chapman, Michael J. Whitekus, Mineko Terao, Enrico Garattini, Oliver Hankinson

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Aldehyde oxidases are a family of highly related molybdo-flavoenzymes acting upon a variety of compounds of industrial and medical importance. We have identified aldehyde oxidase 1 (AOX1) as a 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) inducible gene in the mouse hepatoma cell line Hepa-1. AOX1 mRNA levels were not increased by dioxin in mutant derivatives of the Hepa-1 cell line lacking either functional aryl hydrocarbon receptor (AHR) or aryl hydrocarbon receptor nuclear translocator (ARNT) proteins, thus demonstrating that transcriptional induction of AOX1 in response to dioxin occurs through the AHR pathway. Dioxin induction of AOX1 mRNA was also observed in mouse liver. In addition, levels of AOX1 protein as well as those of aldehyde oxidase homologue 1 (AOH1), a recently identified homolog of AOX1, were elevated in mouse liver in response to dioxin. Employing an aldehyde oxidase specific substrate, AOX1/AOH1 activity was shown to be induced by dioxin in mouse liver. This activity was inhibited by a known inhibitor of aldehyde oxidases, and eliminated by including tungstate in the mouse diet, which is known to lead to inactivation of molybdoflavoenzymes, thus confirming that the enzymatic activity was attributable to AOX1/AOH1. Our observations thus identify two additional xenobiotic metabolizing enzymes induced by dioxin.

Original languageEnglish
Pages (from-to)401-409
Number of pages9
JournalToxicology
Volume207
Issue number3
DOIs
Publication statusPublished - Feb 28 2005

Fingerprint

Aldehyde Oxidase
Dioxins
Genes
Liver
Aryl Hydrocarbon Receptors
Aryl Hydrocarbon Receptor Nuclear Translocator
Cells
Mouse Aox3 protein
Cell Line
Messenger RNA
Xenobiotics
Nutrition
Nuclear Proteins
Hepatocellular Carcinoma

Keywords

  • Aldehyde oxidase
  • Aryl hydrocarbon receptor
  • Dioxin
  • Molybdate

ASJC Scopus subject areas

  • Toxicology

Cite this

Identification of aldehyde oxidase 1 and aldehyde oxidase homologue 1 as dioxin-inducible genes. / Rivera, Steven P.; Choi, Hyun Ho; Chapman, Brett; Whitekus, Michael J.; Terao, Mineko; Garattini, Enrico; Hankinson, Oliver.

In: Toxicology, Vol. 207, No. 3, 28.02.2005, p. 401-409.

Research output: Contribution to journalArticle

Rivera, Steven P. ; Choi, Hyun Ho ; Chapman, Brett ; Whitekus, Michael J. ; Terao, Mineko ; Garattini, Enrico ; Hankinson, Oliver. / Identification of aldehyde oxidase 1 and aldehyde oxidase homologue 1 as dioxin-inducible genes. In: Toxicology. 2005 ; Vol. 207, No. 3. pp. 401-409.
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