Quantitative biology of hydrogen peroxide signaling.
Quantitative biology of hydrogen peroxide signaling.
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DOI：
10.1016/j.redox.2017.04.039
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发表时间：
2017-10
期刊：
影响因子：
11.4
通讯作者：
Brito PM
中科院分区：
文献类型：
--
作者：
Antunes F;Brito PM
过氧化氢（H2O2）通过氧化调节称为氧化还原开关的氧化还原敏感蛋白的活性来控制细胞中的信号传导途径。在这里，定量生物学的概念被应用到审查如何过氧化氢履行信息传输的关键作用。所描述的方程奠定了H2O2信号的基础，给出了H2O2信号机制的新见解，并有助于从常见的氧化还原信号实验中学习新的信息。H2O2信号的一个关键特征是氧化还原开关的还原和氧化之间的比率决定了它们响应的H2O2浓度范围。因此，具有低H2O2依赖性氧化性和缓慢还原速率的氧化还原开关响应于与具有高H2O2依赖性氧化性的氧化还原开关相同的H2O2浓度范围，但是其被快速还原。然而，在第一种情况下，响应时间很慢，而在第二种情况下，响应时间很快。H2O2传感和信息传输可以直接完成，也可以通过复杂的机制完成，其中在氧化最终的调节氧化还原靶之前，氧化在蛋白质之间传递。尽管H2O2是一个非常简单的分子，但它在细胞信号传导中起着关键作用，其传递信息的可靠性取决于氧化还原开关的固有化学反应性、局部H2O2池的存在以及氧化还原开关与其配偶体之间的分子识别。过氧化氢信号通过氧化还原开关的氧化进行。氧化还原开关的氧化可以是直接的或由高反应性传感器介导的。氧化还原开关的响应由其氧化性和还原速率控制。局部蛋白质相互作用确保了信息传递的准确性。
Hydrogen peroxide (H2O2) controls signaling pathways in cells by oxidative modulation of the activity of redox sensitive proteins denominated redox switches. Here, quantitative biology concepts are applied to review how H2O2 fulfills a key role in information transmission. Equations described lay the foundation of H2O2 signaling, give new insights on H2O2 signaling mechanisms, and help to learn new information from common redox signaling experiments. A key characteristic of H2O2 signaling is that the ratio between reduction and oxidation of redox switches determines the range of H2O2 concentrations to which they respond. Thus, a redox switch with low H2O2-dependent oxidability and slow reduction rate responds to the same range of H2O2 concentrations as a redox switch with high H2O2-dependent oxidability, but that is rapidly reduced. Yet, in the first case the response time is slow while in the second case is rapid. H2O2 sensing and transmission of information can be done directly or by complex mechanisms in which oxidation is relayed between proteins before oxidizing the final regulatory redox target. In spite of being a very simple molecule, H2O2 has a key role in cellular signaling, with the reliability of the information transmitted depending on the inherent chemical reactivity of redox switches, on the presence of localized H2O2 pools, and on the molecular recognition between redox switches and their partners. Hydrogen peroxide signaling proceeds through oxidation of redox switches. Oxidation of redox switches can be direct or mediated by highly reactive sensors. Response of redox switches is controlled by their oxidability and reduction rate. Localized protein interactions ensure the accuracy of information transmission.