title: Identification and characterization of functional antioxidant response elements in the promoter of the aldo-keto reductase AKR1B10 gene.
abstract: AKR1B10 is a human-type aldo-keto reductase. The up-regulation of AKR1B10 has been associated with various cancers including non-small cell lung carcinoma, viral and bacterial infections, and skin diseases. However, the mechanisms underlying AKR1B10 gene regulation are not fully understood. We previously indicated the involvement of the transcription factor Nrf2 in AKR1B10 gene regulation. There are at least five potential Nrf2-responsive consensus sequences, so-called antioxidant response elements (AREs), and several ARE-like sequences in the 5'-flanking region up to -3282 bp of the AKR1B10 gene. In the present study, we attempted to identify functional AREs by luciferase reporter analyses using various mutants for each ARE. And we found that only those between -530 and -520 bp (ARE-A), which is the closest location to the translation start site, were functional among the five ARE consensus sites examined. Furthermore, ARE-A functioned co-operatively with the neighboring AP-1 site. Since the AP-1 site resembles ARE, the tandem arrangement of these two elements may be essential for augmented responsiveness to Nrf2 and plays an important role in AKR1B10 gene regulation by various Nrf2-mediating stimuli.
authors.affiliation: Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, Osaka, 584-8540, Japan. Electronic address: nisinat@osaka-ohtani.ac.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Nishinaka
authors.affiliation: Pharmaceutical Education Support Center, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien, 9-Bancho, Nishinomiya, Hyogo, 663-8179, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miura
authors.affiliation: Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, Osaka, 584-8540, Japan.
authors.forename: Kahori
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, Osaka, 584-8540, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Terada
mesh_terms: D000072283:A549 Cells; D000449:Aldehyde Reductase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000074408:Aldo-Keto Reductases; D061745:Antioxidant Response Elements / Q000235:genetics*; D001483:Base Sequence; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D017930:Genes, Reporter; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D011401:Promoter Regions, Genetic
chemical_list: D051267:NF-E2-Related Factor 2; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase
keywords: A549; AP-1; Aldo-keto reductase; Antioxidant response element; H23; Lung; Nrf2; Transcription; c-Jun