Genetic Ablation of Transcription Repressor Bach1 Reduces Neural Tissue Damage and Improves Locomotor Function after Spinal Cord Injury in Mice
Genetic Ablation of Transcription Repressor Bach1 Reduces Neural Tissue Damage and Improves Locomotor Function after Spinal Cord Injury in Mice
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DOI：
10.1089/neu.2008.0667
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发表时间：
2009-01-01
影响因子：
4.2
通讯作者：
Itoi, Eiji
中科院分区：
文献类型：
--
作者：
Kanno, Haruo;Ozawa, Hiroshi;Itoi, Eiji
血红素加氧酶（HO）-1是一种诱导型细胞保护酶，可将血红素降解为铁、一氧化碳（CO）和胆绿素，后两者被认为介导HO-1的抗炎和抗氧化作用。Bach 1是HO-1基因（Hmox-1）的转录抑制因子。先前的报道已经证明，Bach 1的基因切除引起HO-1表达的增加和体内氧化组织损伤程度的显着降低。然而，Bach 1在脊髓损伤中的作用仍不清楚。在本研究中，我们使用Bach 1基因敲除（KO）小鼠和野生型（WT）小鼠在脊髓损伤模型中检查了Bach 1缺陷是否增加HO-1表达并减少神经组织损伤。损伤前后Bach 1基因敲除小鼠脊髓HO-1蛋白表达均显著高于野生型小鼠。在损伤后6周，KO小鼠的运动功能和备用白色物质面积也显著高于WT小鼠。与WT小鼠相比，KO小鼠中受损脊髓中的神经元损失和凋亡性细胞死亡显著减少。这些结果表明，Bach 1缺陷引起组成性更高的HO-1的表达和对脊髓损伤的细胞保护作用显着增加。
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.