Cyclooxygenase-2 as a signaling molecule in radiation-induced bystander effect
Cyclooxygenase-2 as a signaling molecule in radiation-induced bystander effect
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DOI：
10.1002/mc.20219
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发表时间：
2006-06-01
影响因子：
4.6
通讯作者：
Hei, TK
中科院分区：
文献类型：
--
作者：
Hei, TK
辐射诱导的旁观者效应代表着我们对电离辐射的放射生物学效应的理解的范式转变，因为核外和细胞外效应也可能有助于低剂量辐射暴露的最终生物学后果。有证据表明，有针对性的细胞质照射会导致“被击中”细胞的细胞核发生突变，而这些细胞不会被阿尔法粒子直接击中，无论是核子还是细胞质，而是位于被击中的粒子的附近，从而促成了细胞群体的遗传毒性反应。虽然辐射诱导的旁观者效应已经在各种生物系统中得到了很好的证明，但其机制尚不清楚。使用哥伦比亚大学的带电粒子束结合一种新的带电培养皿设计，我们最近证明了环氧合酶-2(COX-2)信号级联在旁观者过程中发挥着重要作用。用抑制COX-2活性的NS-398处理旁观者细胞，显著减少了旁观者效应和丝裂原活化蛋白激酶(MAPK)通路的诱导。这些结果首次证明了COX-2相关通路是旁观者现象的关键信号环节，COX-2在介导细胞炎症反应中是必不可少的。更好地理解旁观者现象的细胞和分子机制，以及它们在体内发生的证据，将使我们能够制定一个更准确的模型来评估低剂量电离辐射对健康的影响。(C)2006年Wiley-Liss，Inc.
Radiation-induced bystander effect represents a paradigm shift in our understanding of the radiobiological effects of ionizing radiation in that extranuclear and extracellular effects may also contribute to the final biological consequences of exposure to low doses of radiation. Evidence suggests that targeted cytoplasmic irradiation results in mutation in the nucleus of the "hit" cells and that cells, which are not directly hit by an alpha particle, whether nuclear or cytoplasm, but are in the vicinity of one that does get hit, contribute to the genotoxic response of the cell population. Although radiation-induced bystander effects have been well documented in a variety of biological systems, the mechanism is not known. Using the Columbia University charged particle beam in conjunction with a novel strip dish design, we showed recently that the cyclooxygenase-2 (COX-2) signaling cascade plays an essential role in the bystander process. Treatment of bystander cells with NS-398, which suppresses COX-2 activity, significantly reduced the bystander effect as well as the induction of the mitogen-activated protein kinase (MAPK) pathways. These results provided the first evidence that the COX-2-related pathway, which is essential in mediating cellular inflammatory responses, is the critical signaling link for the bystander phenomenon. A better understanding of the cellular and molecular mechanisms of the bystander phenomenon together with evidence of their occurrence in vivo will allow us to formulate a more accurate model in assessing the health effects of low doses of ionizing radiation. (c) 2006 Wiley-Liss, Inc.