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.
Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, Japan. sakodae@kure-nh.go.jp
Eiichirou
E
Sakoda
Kazuhiko
K
Igarashi
Jiying
J
Sun
Kaoru
K
Kurisu
Satoshi
S
Tashiro
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