Isolation and analysis of redox regulated transcription factor bound to catalase gene promoter.

活性氧通过对基因表达的不规则控制诱发多种疾病。本研究分离并表征了与大鼠过氧化氢酶基因启动子结合的氧化还原控制转录因子（Box A蛋白），以揭示氧化还原状态转移条件下过氧化氢酶基因转录异常调控的机制。此外，我们发现肝细胞核因子（HNF-3G）是过氧化氢酶基因表达的关键因子。大鼠过氧化氢酶基因启动子在转录起始位点两侧有倒置重复元件。Box A蛋白与元素结合，并被氧化还原调节剂（如过氧化氢）重新排列其结合活性。这个因子组成为。四种蛋白质复合物，这些组分的分子量估计为- 50,38,30。20 kDa。此外，在遗传sopiform脑病大鼠脑中对羟基过氧化氢诱导的神经元细胞死亡进行了分析，发现羟基过氧化氢与氧化还原状态下的Ref- 1蛋白上调有关。另一方面，HNF-3G是一种富集肝细胞的转录因子，是肝细胞分化的决定因素，参与了过氧化氢酶基因表达的调控。携带该基因的重组腺病毒对丧失大部分肝功能的原代肝细胞具有保肝作用。此外，用该载体预处理大鼠肝脏显示出对四氯碳（CCl4）生成的超氧化物等肝损伤试剂的肝保护作用。

Reactive oxygen induces various diseases via an irregular control of gene expressions. In this study, we isolated and characterized redox-controlled transcription factor (Box A protein) bound to the rat catalase gene promoter, in- order to disclose the mechanism for aberrant regulation of catalase gene transcription under the condition of shifted redox state. Moreover, we identified hepatocyte nuclear factor (HNF-3G) as a key factor for catalase gene expression.The rat catalase gene promoter bearded inverted-repeated elements on both sides of transcription initiation site. The Box A protein bound to the elements, and was rearranged the binding activity by redox regulator such as hydroxyl peroxide. This factor composed as. four proteins complex, and the molecular weight of these components were estimated as -50, 38,30. and 20 kDa. Furthermore, hydroxyl peroxide-induced neuronal cell death was analyzed with genetic sopngiform encepharopathy rat brain, and was shown to be involved in upregulation of Ref- 1 protein responded to redox state.On the other hand, HNF-3G, which is a hepatocyte enriched transcription factor and a determinant for differentiation of liver cells, was involved in regulation of catalase gene expression. Recombinant adenovirus carrying this gene showed hepatoconservation effect in the infected primary hepatocyte that lost the most of liver function. Moreover, pretreatment of the rat liver with this vector revealed hepatoprotection effect for hepato-injury regent like a tetrachlorocarbon (CCl4) generating superoxide.