Signalling networks regulating cyclooxygenase-2
Signalling networks regulating cyclooxygenase-2
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DOI：
10.1016/j.biocel.2006.03.021
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发表时间：
2006-01-01
影响因子：
4
通讯作者：
Margioris, Andrew N.
中科院分区：
文献类型：
--
作者：
Tsatsanis, Christos;Androulidaki, Ariadne;Margioris, Andrew N.
环氧合酶-2 （COX-2）是调节前列腺素生成的关键酶，前列腺素是炎症的中枢介质。环氧合酶-2的表达是由几种细胞外信号诱导的，包括促炎和促生长刺激。所有信号都汇聚到丝裂原活化蛋白激酶（MAPK）的激活上，该激酶在转录和转录后水平上调节环氧化酶-2 mRNA的水平。这种机制似乎是高度特化的，包括根据细胞外刺激的类型激活不同的信号分子。环氧化酶-2 mRNA的表达受多种转录因子的调控，包括环amp反应元件结合蛋白（CREB）、核因子κ B （NFkB）和ccaat增强子结合蛋白（C/EBP）。环氧化酶-2转录后也受到mRNA稳定性水平的影响。最后，一氧化氮和一氧化氮合酶（NOS）可以直接影响环加氧酶-2的酶活性。环氧化酶-2调控的每一步都可以作为潜在的治疗靶点。(c) 2006 Elsevier Ltd.版权所有。
Cyclooxygenease-2 (COX-2) is the key enzyme regulating the production of prostaglandins, central mediators of inflammation. The expression of cyclooxygenease-2 is induced by several extra cellular signals including pro-inflammatory and growth-promoting stimuli. All signals converge to the activation of mitogen-activated protein kinases (MAPK) that regulate cyclooxygenease-2 mRNA levels both at the transcriptional and post-transcriptional level. The machinery appears to be highly specialized involving activation of distinct signalling molecules depending on the type of extracellular stimulus. Expression of cyclooxygenease-2 mRNA is regulated by several transcription factors including the cyclic-AMP response element binding protein (CREB), nuclear factor kappa B (NFkB) and the CCAAT-enhancer binding protein (C/EBP). Cyclooxygenease-2 is also affected post-transcriptionaly, at the level of mRNA stability. Finally, cyclooxygenease-2 can be affected directly at its enzymatic activity by nitric oxide and nitric oxide synthase (NOS). Each step of cyclooxygenease-2 regulation can be used as potential therapeutic target. (c) 2006 Elsevier Ltd. All rights reserved.