Lancaster Jack R
Center for Free Radical Biology, Department of Anesthesiology, University of Alabama Birmingham, Birmingham, AL, USA.
Nitric Oxide. 2008 Sep;19(2):68-72. doi: 10.1016/j.niox.2008.04.028. Epub 2008 May 6.
Nitric oxide ((.)NO) has been shown to be a critical player in virtually every aspect of cancer, from tumorigenesis to metastasis. However, as with many aspects of this pluripotent biological mediator in a multitude of physiological and pathophysiological phenomena, the specific mechanisms and pathways that predict its actions are obscure. Much recent interest in the effects of ()NO in the setting of cancer has centered on the possible role of nitrosation (specifically, formation of nitrosothiol, RSNO) as a mechanism of protein-mediated signaling transduction. Here I attempt to show that RSNO formation, although perhaps a reliable marker of reactive nitrogen species (RNS)-induced critical cysteine thiol modification, may not be the functional modification that effects signaling. Kinetic analysis of thiol reactivity with RNS reveals the central position of the thiyl radical (RS(.)), which is a precursor common to several well-established protein cysteine modifications, including nitrosation, dithiol/disulfide exchange, glutathiolation, and oxidation.
一氧化氮（·NO）已被证明在癌症的几乎各个方面都起着关键作用，从肿瘤发生到转移。然而，正如这种多能生物介质在众多生理和病理生理现象中的许多方面一样，预测其作用的具体机制和途径尚不清楚。最近，人们对·NO在癌症环境中的作用的兴趣主要集中在亚硝化作用（特别是亚硝基硫醇，RSNO的形成）作为蛋白质介导的信号转导机制的可能作用上。在这里，我试图表明，RSNO的形成虽然可能是活性氮物种（RNS）诱导的关键半胱氨酸硫醇修饰的可靠标志物，但可能不是影响信号传导的功能修饰。硫醇与RNS反应性的动力学分析揭示了硫自由基（RS·）的中心地位，硫自由基是几种成熟的蛋白质半胱氨酸修饰（包括亚硝化、二硫醇/二硫化物交换、谷胱甘肽化和氧化）共有的前体。
