HYDROGEN PEROXIDE ACTIVATION OF THE STAT PATHWAY

活性氧参与多种疾病，包括 动脉粥样硬化，成人呼吸窘迫综合征，肺纤维化， 和Alfred的。活性氧也具有生理作用， 甚至可以作为细胞代谢的第二信使。几乎 所有的生物体都能迅速激活新的基因 转录反应的氧化应激。一些基因被激活 活性氧是参与解毒这些物种的基因， 如过氧化氢酶和超氧化物歧化酶。在哺乳动物细胞中， 已知参与调节的转录因子 即时早期基因也被活性氧激活。这些包括 NF κ B和AP-1复合物。最近，一个新的转录家族 因子，称为统计（用于信号转导器和激活剂， 转录）已经被描述为介导部分的转录。 对生长因子和细胞因子的转录反应。我们发现 在成纤维细胞中，Stat信号转导通路被激活， 在用过氧化氢处理细胞的五分钟内。 这项提议的目的是阐明激活的机制 的Stat转录因子的H2 O2，并确定基因调控 H2 O2通过Stat转录因子激活。提案的目的 是1）确定氧化还原调节对激活的影响， 通过活性氧统计2）鉴定酪氨酸激酶激活的 H2 O2负责Stat激活和3）了解的作用， 对H2 O2的转录反应中的统计数据。

Reactive oxygen species are involved in a variety of diseases including atherosclerosis, adult respiratory distress syndrome, pulmonary fibrosis, and alzheimer's. Reactive oxygen species also have physiological roles and may even function as second messengers in cellular metabolism. Virtually all living organisms have been found to rapidly activate new gene transcription in response to oxidative stress. Some of the genes activated by reactive oxygen are genes involved in detoxifying these species, such as catalase and superoxide dismutase. In mammalian cells several transcription factors that are known to be involved in the regulation of immediate early genes are also activated by reactive oxygen. These include NF Kappa B and the AP-1 complex. Recently a new family of transcription factors, called Stats (for Signal transducers and activators of transcription) has been described that mediates part of the transcriptional response to growth factors and cytokines.. We have found that in fibroblasts, the Stat signal transduction pathway is activated within five minutes of treatment of cells with hydrogen peroxide. The goals of this proposal are to elucidate the mechanisms of activation of the Stat transcription factors by H2O2 and to identify genes regulated by H2O2 via Stat transcription factor activation. The aims of the proposal are 1) to identify the redox regulatory influences on the activation of Stats by reactive oxygen 2) to identify the tyrosine kinases activated by H2O2 responsible for Stat activation and 3) to understand the role of the Stats in the transcriptional response to H2O2.