Inducible nitric oxide synthase binds, S-nitrosylates, and activates cyclooxygenase-2 (Science, 2005, 310:1966-1970)

報告日期: 2006/03/24
報告時間: 17:10/18:00
報告學生: 陳彥任
講評老師: 凌 斌
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Inducible nitric oxide synthase binds, S-nitrosylates, and activates cyclooxygenase-2

Science 310, 1966-1970 (2005)

 

Speaker陳彥任                                                                                                                                             Time2006/3/24 17:10-18:00

Commentator凌斌 老師                                                   Room602

Abstract

  Inflammatory processes are mediated by multiple molecular mechanisms. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are two major inflammatory mediators. From previous reports showed that inflammatory stimuli elicit the synthesis of iNOS and COX-2 proteins with similar time courses, which suggests that the two systems may interact. In this paper, authors found that iNOS specifically binds to COX-2 in vitro and in intact cells. Then, authors use the biotin switch method as a tool to detect NO-mediated S-nitrosylation of COX-2, they observed that NO donors elicited S-nitrosylation of COX-2 in HEK293T cells expressing COX-2-myc and in RAW264.7 ( murine macrophage ) cells treated with LPS-IFN-γ. This effect was prevented when cells were treated with iNOS inhibitor 1400W. In addition, the S-nitrosylation of COX-2 would enhance COX-2 catalytic activity and increase PGE2 production. Finally, they also found that selectively disrupting iNOS-COX-2 binding prevented NO-mediated activation of COX-2. In summary, a physiologic binding interaction of iNOS and COX-2 bringing NO in proximity to COX-2, facilitating its S-nitrosylation and activation. This synergistic molecular interaction between two inflammatory systems may inform the development of anti-inflammatory drugs.

 

References:

1.      D. Salvemini et al., Nitric Oxide Activates Cyclooxygenase Enzymes Proc. Natl. Acad. Sci. U.S.A. 90, 7240 (1993).

2.      M. E. Turini, R. N. DuBois, Cyclooxygenase-2: a therapeutic target Annu. Rev. Med. 53, 35 (2002).