Regulation of heme oxygenase-1 by transcription factor Bach1 in the mouse brain

Eiichirou Sakoda, Kazuhiko Igarashi, Jiying Sun, Kaoru Kurisu, Satoshi Tashiro

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Oxidative stress has been implicated in tissue damage from traumatic brain injury. Heme oxygenase-1 (HO-1) is an inducible enzyme that degrades prooxidant heme to radical-scavenging biliverdin/bilirubin in order to protect cells from oxidative stress. Although HO-1 is induced after induction of brain damage, the regulatory mechanism of HO-1 in the brain is still unclear. Bach1 is a transcriptional repressor of the HO-1 gene, and plays a critical role in tissue protection from oxidative stress by reperfusion injury of the myocardium. In this study, we examined the role of Bach1 in HO-1 regulation of the various brain sites by investigating the expression of Bach1 and HO-1 in brain tissues of mice bearing Bach1-deficient (Bach1-/-) or wild-type (Bach1+/+) genes. While the expression levels of Bach1 mRNA in the olfactory bulb were significantly higher than other brain areas, those at the cortex showed the lowest activity. Bach1-/- mice showed significantly higher HO-1 mRNA expression levels than Bach1+/+ mice in all brain sites studied. Moreover, higher induction of HO-1 was observed around damaged tissues after cold injury in Bach1-/- than Bach1+/+ mice. Thus, Bach1 plays an important role in regulating the constitutive and inducible expression levels of HO-1 in the brain. Although a significantly higher level of HO-1 was observed in Bach1-/- than Bach1+/+ mice, genetic ablation of the Bach1 gene failed to show any tissue protective effect after cold injury was inflicted on the cortex.

Original languageEnglish
Pages (from-to)160-165
Number of pages6
JournalNeuroscience Letters
Volume440
Issue number2
DOIs
Publication statusPublished - 2008 Aug 1

Keywords

  • Bach1
  • Brain
  • Cold injury model
  • Heme oxygenase-1
  • Transcription factor

ASJC Scopus subject areas

  • Neuroscience(all)

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