Regulation of heme oxygenase-1 by transcription factor Bach1 in the mouse brain.
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.
Sakoda
Eiichirou
E
Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, Japan. sakodae@kure-nh.go.jp
Igarashi
Kazuhiko
K
Sun
Jiying
J
Kurisu
Kaoru
K
Tashiro
Satoshi
S
D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009830:Olfactory Bulb / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology
C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D012333:RNA, Messenger; D014157:Transcription Factors; D051547:Heme Oxygenase-1