Genetic ablation of the transcription repressor Bach1 leads to myocardial protection against ischemia/reperfusion in mice

Yoko Yano, Ryoji Ozono, Yoshihiko Oishi, Masayuki Kambe, Masao Yoshizumi, Takafumi Ishida, Shinji Omura, Tetsuya Oshima, Kazuhiko Igarashi

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59 Citations (Scopus)

Abstract

Bach1 is a transcriptional repressor of heme oxygenase-1 gene (Hmox-1) and β-globin gene. Heme oxygenase (HO)-1 is an inducible cytoprotective enzyme that degrades pro-oxidant heme to carbon monoxide (CO) and biliverdin/bilirubin, which are thought to mediate anti-inflammatory and anti-oxidant actions of HO-1. In the present study, we investigated the role of Bach1 in tissue protection against myocardial ischemia/reperfusion (I/R) injury in vivo using mice lacking the Bach1 gene (Bach1-/-) and wild-type (Bach1+/+) mice. In Bach1-/- mice, myocardial expression of HO-1 protein was constitutively up-regulated by 3.4-fold compared to that in Bach1+/+ mice. While myocardial I/R induced HO-1 protein in ischemic myocytes in both strains of mice, the extent of induction was significantly greater in Bach1-/- mice than in Bach1+/+ mice. Myocardial infarction was markedly reduced in size by 48.4% in Bach1-/- mice. Pretreatment of Bach1-/- mice with zinc-protoporphyrin, an inhibitor of HO activity, abolished the infarction-reducing effect of Bach1 disruption, indicating that reduction in the infarct size was mediated, at least in part, by HO-1 activity. Thus, Bach1 plays a pivotal role in setting the levels of both constitutive and inducible expression of HO-1 in the myocardium. Bach1 inactivation during I/R appears to be a key mechanism controlling the activation level of cytoprotective program involving HO-1.

Original languageEnglish
Pages (from-to)791-803
Number of pages13
JournalGenes to Cells
Volume11
Issue number7
DOIs
Publication statusPublished - 2006 Jul 1

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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