NF-B 信号通路保护肝损伤作用研究进展,专业： 年级： 姓名： 导师：,细胞信号转导课程报告,细胞信号转导课程报告,肝炎通常是指由多种致病因素-如病毒、细菌、寄生虫、化学毒物、药物、酒精、自身免疫因素等使肝脏细胞受到破坏，肝脏的功能受到损害，引起身体一系列不适症状，以及肝功能指标的异常。 由病毒造成的肝炎能引起肝脏细胞肿胀，是世界上流传广泛，危害很大的传染病之一,细胞信号转导课程报告,细胞信号转导课程报告,NF-B ：几乎存在于所有类型的动物细胞中并参与细胞对诸多刺激的响应，这些刺激包括应激、细胞因子、自由基、紫外线照射、氧化LDL及细菌或病毒抗原,NF-B信号通路,核因子-kB(NF-kB)抑制物(I-kB)的激酶,细胞信号转导课程报告,Nuclear factor-kappa B (NF-kB) activation signaling pathway.,B Sun and M Karin , 2008 Oncogene,细胞信号转导课程报告,Crosstalking between apoptosis and nuclear factor-kappa B (NF-kB) signaling.,B Sun and M Karin , 2008 Oncogene,The antiapoptotic effect can be carried out by NF-kB targeting genes including Bcl-2 family, TRAF2, CIAP,FLIP and A-20, which has antiapoptosis effect by either re-activating NF-kB signaling or blocking signal transduction as anegative feedback to activation of apoptosis.,非Caspase 诱导凋亡途径,细胞信号转导课程报告,NF-kB has an important role in liver physiology and function.,Makris et al., 2000 ，Molecular Cell,Severe Dermatopathy in Ikk+/ Female Mice,细胞信号转导课程报告,NF-kB has an important role in liver physiology and function.,Massive liver apoptosis in the absence of NEMO/IKK,Rudolph et al., 2000 Genes & Development,细胞信号转导课程报告,NF-kB has an important role in liver physiology and function.,Li et al., 1999 Science,Liver phenotype in IKK/embryos at E13,RelA-,IKKb- and IKKg- knockout mice die around embryonicdays 12.514.5,细胞信号转导课程报告,NF-kB has an important role in liver physiology and function.,In contrast,IKKa knockout mice survive until birth,Takeda et al., 1999 Science,细胞信号转导课程报告,IKK/NEMO is the essential regulatory subunit of the IB kinase (IKK), It is required for NF-B activation and resistance to TNF-induced apoptosis. IKKa is not required for protection from TNFa-induced liver apoptosis.,NF-kB has an important role in liver physiology and function.,细胞信号转导课程报告,NF-kB has an important role in liver physiology and function.,Ikkhep Mice Are More Sensitive to LPS+GalN,Maeda et al., 2003 Immunity,细胞信号转导课程报告,NF-kB has an important role in liver physiology and function.,Maeda et al., 2003 Immunity,Ikkhep Mice Display a Marked Increase in Sensitivity to ConA-Induced Liver Damage,JNK1-deficient mice are resistant to ConA-induced liver failure Chang et al., 2006 Cell,细胞信号转导课程报告,NF-kB has an important role in liver physiology and function.,近年来研究发现，预防或者阻止TNFa 引起的细胞损伤，有一种非常关键的因子c-FLIP，它是一种抗凋亡蛋白，由NF-kB 转录而来，但是却能被JNK1 降解。,Chang et al., 2006 Cell,TNFa Induces JNK1-Dependent c-FLIP Degradation,细胞信号转导课程报告,因此， NF-kB 通过维持c-FLIP的高水平表达，来促进肝细胞的存活以及肝脏器官的完整性。,TNFa-Induced Apoptosis Depends on Itch Activa-tion by JNK1 and c-FLIPL Degradation,Chang et al., 2006 Cell,细胞信号转导课程报告,Thanks！,