Reactive nitrogen species block cell cycle re-entry through sustained production of hydrogen peroxide.
Reactive nitrogen species block cell cycle re-entry through sustained production of hydrogen peroxide.
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DOI：
10.1165/rcmb.2002-0112oc
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发表时间：
2003-01
影响因子：
6.4
通讯作者：
Ziqiang Yuan;H. Schellekens;L. Warner;Y. Janssen-Heininger;P. Burch;N. Heintz
中科院分区：
文献类型：
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作者：
Ziqiang Yuan;H. Schellekens;L. Warner;Y. Janssen-Heininger;P. Burch;N. Heintz
内源性活性氮物质（RNS）作为第二信使参与多种细胞信号传导，而环境源的RNS如二氧化氮（NO2）通过共价修饰细胞大分子抑制细胞存活和生长。为了研究RNS对细胞周期进程的影响，小鼠II型肺泡C10细胞在G 0血清剥夺被捕暴露于NO2或SIN-1，RNS的发电机，在细胞周期重新进入。在血清刺激的细胞中，RNS没有阻止AP-1的立即早期基因反应，而是阻断细胞周期蛋白D1基因表达，导致细胞周期停滞在G 0和G1之间的边界。二氯荧光素二乙酸酯（DCF）的荧光表明，RNS诱导持续生产的细胞内过氧化氢（H2 O2），这通常是只产生短暂的血清生长因子。用过氧化氢酶加载细胞并没有减少细胞表面3-硝基酪氨酸的形成，而是阻止了DCF荧光增强，挽救了细胞周期蛋白D1的表达和S期进入。这些研究表明，环境RNS干扰细胞周期的重新进入，通过过氧化氢依赖的机制，影响细胞周期蛋白D1的表达和进展，从G 0到G1期的细胞周期。
Endogenous sources of reactive nitrogen species (RNS) act as second messengers in a variety of cell signaling events, whereas environmental sources of RNS like nitrogen dioxide (NO2) inhibit cell survival and growth through covalent modification of cellular macromolecules. To examine the effects of RNS on cell cycle progression, murine type II alveolar C10 cells arrested in G0 by serum deprivation were exposed to either NO2 or SIN-1, a generator of RNS, during cell cycle re-entry. In serum-stimulated cells, RNS did not prevent the immediate early gene response by AP-1, but rather blocked cyclin D1 gene expression, resulting cell cycle arrest at the boundary between G0 and G1. Dichlorofluorescin diacetate (DCF) fluorescence indicated that RNS induced sustained production of intracellular hydrogen peroxide (H2O2), which normally is produced only transiently in response to serum growth factors. Loading cells with catalase did not diminish the formation of 3-nitrotyrosine on the cell surface, but rather prevented enhanced DCF fluorescence and rescued cyclin D1 expression and S phase entry. These studies indicate environmental RNS interfere with cell cycle re-entry through an H2O2-dependent mechanism that influences expression of cyclin D1 and progression from G0 to the G1 phase of the cell cycle.