Aldehyde oxidase 1 gene is regulated by Nrf2 pathway.
Aldehyde oxidase is a member of the molybd-flavo enzyme family that catalyzes the hydroxylation of heterocycles and the oxidation of aldehydes into corresponding carboxylic acids. Aldehyde oxidase-1 (AOX1) is highly expressed in liver and is involved in the oxidation of a variety of aldehydes and nitrogenous heterocyclic compounds, including anti-cancer and immunosuppressive drugs. However, the physiological substrates of AOX1 have not been identified, and it was unknown how the expression of AOX1 is regulated. Here, we found that the AOX1 gene is regulated by the Nrf2 pathway. Two Nrf2 binding consensus elements (antioxidant responsive element, ARE) are located in the 5' upstream region of the rat AOX1 gene. Molecular analyses using reporter transfection analysis, EMSA, and ChIP analysis show that Nrf2 binds to and strongly activates the rat AOX1 gene.
Division of Radiological Technology, Department of Health Sciences, School of Medicine, Hokkaido University, Kita-12, Nishi-5, Sapporo 060-0812, Japan.
Kenichiro
K
Maeda
Takashi
T
Ohno
Shizuka
S
Igarashi
Takaaki
T
Yoshimura
Koji
K
Yamashiro
Masaharu
M
Sakai
D042931:Aldehyde Oxidase / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic; D008099:Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D015533:Transcriptional Activation
D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D042931:Aldehyde Oxidase; C539015:Aox1protein, rat