Identification of aldehyde oxidase 1 and aldehyde oxidase homologue 1 as dioxin-inducible genes.
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.
Rivera
Steven P
SP
Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, University of California, 650 Charles E. Young Dr., Factor Bldg. 13-230, Los Angeles, CA 90095-1732, USA.
Choi
Hyun Ho
HH
Chapman
Brett
B
Whitekus
Michael J
MJ
Terao
Mineko
M
Garattini
Enrico
E
Hankinson
Oliver
O
D000445:Aldehyde Oxidoreductases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004032:Diet; D004359:Drug Therapy, Combination; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D010940:Plant Proteins; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000172:deficiency / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics; D017973:Tungsten Compounds / Q000008:administration & dosage; D000099188:Alternative Oxidase
D000445:Aldehyde Oxidoreductases; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D004268:DNA-Binding Proteins; D004785:Environmental Pollutants; D004791:Enzyme Inhibitors; D024101:Mitochondrial Proteins; D010088:Oxidoreductases; D010940:Plant Proteins; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D017973:Tungsten Compounds; D000099188:Alternative Oxidase; C497397:Arnt protein, mouse; C443116:Aox3 protein, mouse; C045951:tungstate