TY - JOUR
T1 - Regulation of heme oxygenase-1 by transcription factor Bach1 in the mouse brain
AU - Sakoda, Eiichirou
AU - Igarashi, Kazuhiko
AU - Sun, Jiying
AU - Kurisu, Kaoru
AU - Tashiro, Satoshi
N1 - Funding Information:
We are grateful to N. Osumi and K. Sakurai (Tohoku University, Graduate School of Medicine) for their technical advice. This work was supported by the Ministry of Education, Culture, Sports, Science and Technology, Japan.
PY - 2008/8/1
Y1 - 2008/8/1
N2 - 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.
AB - 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.
KW - Bach1
KW - Brain
KW - Cold injury model
KW - Heme oxygenase-1
KW - Transcription factor
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U2 - 10.1016/j.neulet.2008.04.082
DO - 10.1016/j.neulet.2008.04.082
M3 - Article
C2 - 18555605
AN - SCOPUS:45449084790
SN - 0304-3940
VL - 440
SP - 160
EP - 165
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 2
ER -