title: Genetic ablation of transcription repressor Bach1 reduces neural tissue damage and improves locomotor function after spinal cord injury in mice.
abstract: Heme oxygenase (HO)-1 is an inducible cytoprotective enzyme that degrades heme to iron, carbon monoxide (CO), and biliverdin, the latter two of which are thought to mediate the anti-inflammatory and antioxidant actions of HO-1. Bach1 is a transcriptional repressor of the HO-1 gene (Hmox-1). Previous reports have demonstrated that the genetic ablation of Bach1 engenders an increased HO-1 expression and a marked reduction in the degree of oxidative tissue damage in vivo. However, the function of Bach1 in spinal cord injury is still not understood. In the present study, we examined whether Bach1 deficiency increases HO-1 expression and reduces neural tissue damage in a spinal cord injury model using Bach1 knock-out (KO) mice and wild-type (WT) mice. The expression of HO-1 protein in the spinal cord was significantly higher in the Bach1 KO mice than in the WT mice before and after injury. The KO mice also had significantly higher Basso mouse scale scores for locomotor function and larger areas of spared white matter than the WT mice at 6 weeks after injury. Neuronal loss and apoptotic cell death in the injured spinal cord was significantly reduced in the KO mice in comparison to the WT mice. These results suggest that Bach1 deficiency engenders a constitutively higher expression of HO-1 and a dramatic increase in cytoprotection against spinal cord injury.
authors.affiliation: Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, Japan. kanno-h@isis.ocn.ne.jp
authors.forename: Haruo
authors.initials: H
authors.lastname: Kanno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ozawa
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Dohi
authors.forename: Akira
authors.initials: A
authors.lastname: Sekiguchi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Igarashi
authors.forename: Eiji
authors.initials: E
authors.lastname: Itoi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics*; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D051547:Heme Oxygenase-1 / Q000235:genetics; D020287:In Situ Nick-End Labeling; D007794:Lameness, Animal / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism; D020127:Recovery of Function / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D013116:Spinal Cord / Q000378:metabolism* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D015415:Biomarkers; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D012097:Repressor Proteins; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; C505409:Casp3 protein, mouse; D053148:Caspase 3