Nrf2的建立在表皮细胞保护作用的UVB谷胱甘肽-介导的梯度.doc

Nrf2的建立在表皮细胞保护作用的UVB谷胱甘肽-介导的梯度 Matthias Sch?fer 1 , 5 , 马蒂亚斯舍费尔 1 ， 5 ， Sabine Dütsch 1 , 萨宾Dütsch 1 ， Ulrich auf dem Keller 1 , 乌尔里希奥夫DEM凯勒 1 ， Fatemeh Navid 2 , Fatemeh纳维德哈尼 2 ， Agatha Schwarz 2 , 阿加莎施瓦茨 2 ， Delinda A. Johnson 3 , Delinda A.约翰逊 3 ， Jeffrey A. Johnson 3 and 杰弗里A ·约翰逊 3 Sabine Werner 1 , 4 萨宾沃纳 1 ， 4 + Author Affiliations 1 Department of Biology, Institute of Cell Biology, ETH Zurich, CH-8093 Zurich, Switzerland; 1生物系细胞生物学研究所，苏黎世联邦理工学院，苏黎世CH - 8093，瑞士; 2 Department of Dermatology, Christian-Albrechts-University of Kiel, D-24105 Kiel, Germany;皮肤科，基督教- Albrechts，D - 24105 Kiel，德国基尔大学的 2部; 3 University of Wisconsin, School of Pharmacy, Madison, Wisconsin 53705, USA 3，药房，麦迪逊，威斯康星大学，美国威斯康星州53705 Next Section 下一节 Abstract摘要 Ultraviolet (UV) B irradiation can severely damage the skin and even induce tumorigenesis.紫外线（UV）B辐射可能会严重伤害皮肤，甚至诱发肿瘤的发生。 It exerts its effects by direct DNA modification and by formation of reactive oxygen species (ROS).它施加直接的DNA修饰和活性氧（ROS）的形成及其影响。 We developed a strategy to genetically activate target gene expression of the transcription factor NF-E2-related factor 2 (Nrf2) in keratinocytes in vivo based on expression of a constitutively active Nrf2 mutant.我们开发的战略目标基因表达的转录因子NF - E2相关因子2（Nrf2的）角质形成细胞在体内的基础上表达的一个组成性激活Nrf2的突变基因激活。 Activation of Nrf2 target genes strongly reduced UVB cytotoxicity through enhancement of ROS detoxification. Nrf2的靶基因的激活，大大减少紫外线B的细胞毒作用，通过提高ROS的解毒。 Remarkably, the protective effect was extended to neighboring cells.值得注意的是，扩展到邻近的细胞保护作用。 Using different combinations of genetically modified mice, we demonstrate that Nrf2 activates the production, recycling, and release of glutathione and cysteine by suprabasal keratinocytes, resulting in protection of basal cells in a paracrine, glutathione/cysteine-dependent manner.使用转基因小鼠的不同组合，我们证明Nrf2的激活基底层角质形成细胞的谷胱甘肽和半胱氨酸的生产，回收，释放，保护基底细胞的旁分泌，谷胱甘肽/半胱氨酸的依赖性。 Most importantly, we found that endogenous Nrf2 controls selective protection of suprabasal keratinocytes f