核因子κB(Nuclear Factor κB,NF-κB):一个新的治疗目标

被引:1
作者
冷启新
hotmail.com
刘执玉
李瑞祥
机构
[1] 潍坊医学院!潍坊qixinleng
[2] 山东医科大学!济南
[3] 华西医科大学!成都
关键词
B; NF; 蛋白; 磷酸化; 基因; 调控; TRAF; 调节控制; Nuclear Factor; 核因子; IKK;
D O I
10.16695/j.cnki.1006-2947.1999.04.001
中图分类号
R394.8 [医学遗传工程];
学科分类号
0831 ;
摘要
NF- κ B是一个广泛存在于细胞 ,调控许多细胞因子、化学趋化因子、细胞粘附分子、生长因子、免疫受体等的转录因子 ,也是参与机体免疫炎症反应的快速反应因子。 NF-κ B的过度表达与许多疾病如 :感染性休克、风湿性关节炎、支气管哮喘、动脉粥样硬化、溃疡性结肠炎、老年性痴呆、AIDS等的免疫病理机制有关。正常情况下 ,NF- κ B以无活性状态存在于胞浆中 ,它是由 NF- κ B1和 Rel构成的二聚体 ,与其抑制蛋白( Inhibitoryκ B,IκB)结合形成的三聚体。细胞外的许多信号可激活 NF- κ B,首先引起 NF- κ B诱导激酶 ( NF-κ B inducing kinase,NIK)的活化 ,继而活化 IκB激酶 ( IκB kinase,IKK) ,使 IκB磷酸化 ,编在蛋白化 ,蛋白酶解 ,IκB从 NF-κ B复合体上脱落 ,活化的 NF-κ B,通过核孔进入到细胞核 ,结合到靶基因的κ结构域 ,引起相应基因的转录。 NF-κ B的活化过程可被许多因素抑制 ,特殊的干预治疗在于通过抗氧化剂、蛋白酶抑制剂抑制 NIK和 IKK的活化、诱导内毒素耐受和应用皮质激素通过直接与 NF- κ B结合或上调 IκB的表达。反义NF- κ B和转录因子假结合体 ( Transcription Factor Decoy,TFD)为与 NF- κ B过度活化有关疾病的基因治疗提供了新的思路 ,新的更特异、更有效的抑制将有待进一
引用
收藏
页码:289 / 295
页数:7
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