p38MAPK介导的胶质细胞iNOS的转录激活机制

被引:5
作者
沈勤
张然
吴扬
施建华
机构
[1] 南通大学基础医学院生物化学与分子生物学教研室,DepartmentofNeurologyMedicineUniversityofSouthCarolinaCharleston,SC,USA,南通大学基础医学院航海医学研究所,南通大学基础医学院生物化学与分子生物学教研室江苏省南通市,江苏省南通市,江苏省南通市
关键词
p38MAPK; 转录因子; 可诱导型氧化氮合酶; 胶质细胞; 瞬时转染;
D O I
10.13865/j.cnki.cjbmb.2005.03.006
中图分类号
R33 [人体生理学];
学科分类号
1001 ;
摘要
丝裂原激活蛋白激酶(MAPK)酶级联反应系统参与胶质细胞中iNOS的合成.通过瞬时转染p38MAPK途径中上游激酶,MAPK激酶3(MKK3)和MAPK激酶6 (MKK6 )表达质粒,进一步了解p38MAPK级联传导信号系统调节iNOS基因在胶质细胞中的转录激活机制.MKK3或MKK6表达质粒与接有荧光素酶(luciferase ,Luc)的大鼠iNOS启动基因质粒(iNOS Luc)联合转染C6星形胶质细胞株引起iNOS Luc的激活,并且使细胞因子诱导的iNOSmRNA的表达增强.这两种效应都能够被p38MAPK抑制剂SB2 0 35 80所抑制.MKK3 6也可以诱导核因子κB(NFκB Luc)依赖的转录活性.这些分子水平的研究结果为p38MAPK信号级联传导途径在调节大鼠胶质细胞中iNOS基因转录激活中的重要作用,包括转录因子NFκB的作用提供了证据.通过阻断iNOS表达或NO的生成,抑制细胞炎症发生,为防治神经细胞炎症反应性疾病提供实验依据.
引用
收藏
页码:315 / 321
页数:7
相关论文
共 16 条
[1]  
Molecular cloning and analysis of the rat inducible nitric oxide synthase gene promoter in aortic smooth muscle cells. Zhang H F,Chen X S,Teng X W,Snead C,Catravas J D. Biochemical Pharmacology . 1998
[2]  
Nitric oxide in neuronal degeneration. Dawson V L,Dawson TM. Proceedings of the Society for Experimental Biology and Medicine . 1996
[3]  
The p38 signal transduction pathway: activation and function. Ono K,Han J. Cellular Signalling . 2000
[4]   丝裂原活化蛋白激酶(MAPK)生物学功能的结构基础 [J].
龚小卫 ;
姜勇 .
中国生物化学与分子生物学报, 2003, (01) :5-11
[5]  
Taxol activates inducible nitric oxide synthase in rat astrocytes: the role of MAP kinases and NF-κB[J] . I. Cvetkovic,D. Miljkovic,O. Vuckovic,L. Harhaji,Z. Nikolic,V. Trajkovic,M. Mostarica Stojkovic. &nbspCellular and Molecular Life Sciences . 2004 (10)
[6]   The role of nitric oxide in multiple sclerosis [J].
Parkinson, JF ;
Mitrovic, B ;
Merrill, JE .
JOURNAL OF MOLECULAR MEDICINE-JMM, 1997, 75 (03) :174-186
[7]  
INOS-mediated nitric oxide production and its regulation. Aktan F. Life Sciences . 2004
[8]  
CCAAT enhancer binding protein-beta transactivates murine nitric oxide synthase 2 gene in an MTAL cell line. Gupta A K,Kone B C. American Journal of Physiology . 1999
[9]  
The role of nitric oxide in multiple sclerosis. Parkinson J F,Mitrovic B,Merrill J E. Journal of Molecular Medicine . 1997
[10]  
The Toll-receptor family and control of innate immunity. Kopp E B,Medzhitov R. Current Opinion in Immunology . 1999