title: Potential role of heme metabolism in the inducible expression of heme oxygenase-1.
abstract: The degradation of heme significantly contributes to cytoprotective effects against oxidative stress and inflammation. The enzyme heme oxygenase-1 (HO-1), involved in the degradation of heme, forms carbon monoxide (CO), ferrous iron, and bilirubin in conjunction with biliverdin reductase, and is induced by various stimuli including oxidative stress and heavy metals. We examined the involvement of heme metabolism in the induction of HO-1 by the inducers sulforaphane and sodium arsenite.
  
  
  
  We examined the expression of HO-1 in sulforaphane-, sodium arsenite- and CORM3-treated HEK293T cells, by measuring the transcriptional activity and levels of mRNA and protein.
  
  
  
  The blockade of heme biosynthesis by succinylacetone and N-methyl protoporphyrin, which are inhibitors of heme biosynthesis, markedly decreased the induction of HO-1. The knockdown of the first enzyme in the biosynthesis of heme, 5-aminolevulinic acid synthase, also decreased the induction of HO-1. The cessation of HO-1 induction occurred at the transcriptional and translational levels, and was mediated by the activation of the heme-binding transcriptional repressor Bach1 and translational factor HRI. CO appeared to improve the expression of HO-1 at the transcriptional and translational levels.
  
  
  
  We demonstrated the importance of heme metabolism in the stress-inducible expression of HO-1, and also that heme and its degradation products are protective factors for self-defense responses.
  
  
  
  The key role of heme metabolism in the stress-inducible expression of HO-1 may promote further studies on heme and its degradation products as protective factors of cellular stresses and iron homeostasis in specialized cells, organs, and whole animal systems.
authors.affiliation: Department of Biotechnology, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8510, Japan.
authors.forename: Taka-Aki
authors.initials: TA
authors.lastname: Takeda
authors.affiliation: Department of Biotechnology, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8510, Japan.
authors.forename: Machiko
authors.initials: M
authors.lastname: Sasai
authors.affiliation: Department of Biotechnology, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8510, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Adachi
authors.affiliation: Department of Biotechnology, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8510, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ohnishi
authors.affiliation: Department of Microbiology, Kansai Medical University, Hirakata, Osaka 573-8510, Japan.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Fujisawa
authors.affiliation: Department of Biotechnology, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8510, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Izawa
authors.affiliation: Department of Biotechnology, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8510, Japan; Unit of Research Complex, Kansai Medical University, Hirakata, Osaka 573-8510, Japan. Electronic address: taketans@hirakata.kmu.ac.jp.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Taketani
mesh_terms: D018053:Arsenites / Q000494:pharmacology; D050976:Basic-Leucine Zipper Transcription Factors / Q000502:physiology; D002248:Carbon Monoxide / Q000502:physiology; D004790:Enzyme Induction; D051856:Fanconi Anemia Complementation Group Proteins / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D006418:Heme / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics*; D006537:Heptanoates / Q000494:pharmacology; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology; D017670:Sodium Compounds / Q000494:pharmacology; D013454:Sulfoxides
chemical_list: D018053:Arsenites; C102108:BACH1 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D051856:Fanconi Anemia Complementation Group Proteins; D006537:Heptanoates; D017879:Isothiocyanates; D011524:Protoporphyrins; D017670:Sodium Compounds; D013454:Sulfoxides; D006418:Heme; C017947:sodium arsenite; C020804:succinylacetone; C028842:N-methylprotoporphyrin IX; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1; C016766:sulforaphane
keywords: Bach1; CORM3; HO-1; HRI; Heme metabolism; Sulforaphane