Inducible nitric oxide synthase binds, S-nitrosylates, and activates cyclooxygenase-2

被引:429
作者
Kim, SF
Huri, DA
Snyder, SH
机构
[1] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA
关键词
D O I
10.1126/science.1119407
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are two major inflammatory mediators. Here we show that iNOS specifically binds to COX-2 and S-nitrosylates it, enhancing COX-2 catalytic activity. Selectively disrupting iNOS-COX-2 binding prevented NO-mediated activation of COX-2. This synergistic molecular interaction between two inflammatory systems may inform the development of anti-inflammatory drugs.
引用
收藏
页码:1966 / 1970
页数:5
相关论文
共 23 条
[1]  
Appleton I, 1996, Adv Pharmacol, V35, P27, DOI 10.1016/S1054-3589(08)60274-4
[2]  
BRAUGHLER JM, 1979, J BIOL CHEM, V254, P2450
[3]   Dexras1: A G protein specifically coupled to neuronal nitric oxide synthase via CAPON [J].
Fang, M ;
Jaffrey, SR ;
Sawa, A ;
Ye, KQ ;
Luo, XJ ;
Snyder, SH .
NEURON, 2000, 28 (01) :183-193
[4]   The development of COX2 inhibitors [J].
Flower, RJ .
NATURE REVIEWS DRUG DISCOVERY, 2003, 2 (03) :179-191
[5]   The structure of mammalian cyclooxygenases [J].
Garavito, RM ;
Mulichak, AM .
ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE, 2003, 32 :183-206
[6]   Protein S-nitrosylation:: Purview and parameters [J].
Hess, DT ;
Matsumoto, A ;
Kim, SO ;
Marshall, HE ;
Stamler, JS .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2005, 6 (02) :150-166
[7]   Protein S-nitrosylation:: a physiological signal for neuronal nitric oxide [J].
Jaffrey, SR ;
Erdjument-Bromage, H ;
Ferris, CD ;
Tempst, P ;
Snyder, SH .
NATURE CELL BIOLOGY, 2001, 3 (02) :193-197
[8]  
JAFFREY SR, 2001, SCI STKE, pP61
[9]  
KENNEDY TA, 1994, J BIOL CHEM, V269, P27357
[10]   DOMAIN INTERACTION BETWEEN NMDA RECEPTOR SUBUNITS AND THE POSTSYNAPTIC DENSITY PROTEIN PSD-95 [J].
KORNAU, HC ;
SCHENKER, LT ;
KENNEDY, MB ;
SEEBURG, PH .
SCIENCE, 1995, 269 (5231) :1737-1740