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

活性氧通过基因表达的不规则控制诱导各种疾病。本研究分离并鉴定了与大鼠过氧化氢酶基因启动子结合的氧化还原调控转录因子（Box A蛋白），旨在揭示氧化还原状态改变条件下过氧化氢酶基因转录的异常调控机制。此外，我们还发现肝细胞核因子（hepatocyte nuclear factor，HNF-3G）是过氧化氢酶基因表达的关键因子。Box A蛋白与元素结合，并通过氧化还原调节剂如过氧化氢重排结合活性。这个因素组成为。4种蛋白质复合物，分子量分别为-50，38，30。20 kDa。此外，用遗传性索状脑病大鼠脑组织分析了过氧化氢诱导的神经元细胞死亡，结果表明，过氧化氢诱导的神经元细胞死亡与氧化还原状态下Ref- 1蛋白表达上调有关，而肝细胞富集的转录因子HNF-3G参与过氧化氢酶基因表达的调节。携带该基因的重组腺病毒对感染后肝功能大部分丧失的原代肝细胞有保护作用。此外，用该载体预处理大鼠肝脏显示了对肝损伤试剂如产生超氧化物的四氯化碳（CCl 4）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.