title: Bach1-dependent and -independent regulation of heme oxygenase-1 in keratinocytes.
abstract: Bach1 is a member of the basic leucine zipper transcription factor family, and the Bach1/small Maf heterodimer specifically represses transcriptional activity directed by the Maf recognition element (MARE). Because Bach1 is a repressor of the oxidative stress response, we examined the function(s) of Bach1 in keratinocytes subjected to oxidative stress. Oxidative stress induced by H(2)O(2) led to an increase in MARE activity and expression of heme oxygenase-1 (HO-1), an inducible antioxidant defense enzyme. Bach1 depletion by small interfering RNAs or by deletion of Bach1 enhanced HO-1 expression in the absence of H(2)O(2), indicating that Bach1 is a critical repressor of HO-1 in keratinocytes. Although Bach1-deficient or -reduced keratinocytes expressed higher levels of HO-1 than control cells in response to H(2)O(2), Bach1 down-regulation did not attenuate the production of reactive oxygen species by H(2)O(2). In contrast, Bach1 overexpression abolished HO-1 induction by H(2)O(2), which led to increased reactive oxygen species accumulation. HO-1 was induced during keratinocyte differentiation, but MARE activity did not change during differentiation. Furthermore, Bach1 overexpression did not inhibit differentiation-associated induction of HO-1 expression, suggesting that HO-1 induction in differentiation is independent of Bach1. Thus, in response to oxidative stress, Bach1 regulates the oxidation state through the negative control of HO-1 expression prior to terminal keratinocyte differentiation. However, Bach1-mediated repression is negated during keratinocyte differentiation.
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors.forename: Shuko
authors.initials: S
authors.lastname: Okada
authors.forename: Akihiko
authors.initials: A
authors.lastname: Muto
authors.forename: Eisaku
authors.initials: E
authors.lastname: Ogawa
authors.forename: Ayako
authors.initials: A
authors.lastname: Nakanome
authors.forename: Yasutake
authors.initials: Y
authors.lastname: Katoh
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Ikawa
authors.forename: Setsuya
authors.initials: S
authors.lastname: Aiba
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Igarashi
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Okuyama
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004817:Epidermis / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology*; D051379:Mice; D008813:Mice, Inbred ICR; D008954:Models, Biological; D018384:Oxidative Stress
chemical_list: D000975:Antioxidants; C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1