Department of Pharmacology, Georgetown University Medical Center, Washington, DC, USA.
Antioxid Redox Signal. 2010 Mar;12(3):393-404. doi: 10.1089/ars.2009.2805.
Reactive oxygen species (ROS) serve as mediators of signal transduction. However, mechanisms of how ROS influence the target molecules to elicit signaling event have not been defined. Our laboratory recently accumulated evidence for the role of protein carbonylation in the mechanism of ROS signaling. This concept originated from experiments in which pulmonary artery smooth muscle cells were treated with endothelin-1 to understand the mechanism of cell growth. Endothelin-1 was found to promote protein carbonylation in an endothelin receptor- and Fenton reaction-dependent manner. Mass spectrometry identified proteins that are carbonylated in response to endothelin-1, including annexin A1. Our experiments generated a hypothesis that endothelin-1-mediated carbonylation and subsequent degradation of annexin A1 promote cell growth. This mechanism was found also to occur in response to other signaling activators such as serotonin and platelet-derived growth factor in smooth muscle cells of pulmonary circulation, systemic circulation, and the airway, as well as in cardiac muscle cells, suggesting the universal role of this pathway. We also discovered a process of decarbonylation that defines transient kinetics of carbonylation signals in certain conditions. We propose that protein carbonylation and decarbonylation serve as a mechanism of signal transduction.
活性氧（ROS）作为信号转导的介质。然而，ROS 如何影响靶分子以引发信号事件的机制尚未确定。我们实验室最近积累了证据，证明蛋白质羰基化在 ROS 信号机制中的作用。这一概念源于我们用内皮素-1 处理肺动脉平滑肌细胞以了解细胞生长机制的实验。研究发现，内皮素-1 以依赖内皮素受体和 Fenton 反应的方式促进蛋白质羰基化。质谱鉴定出对内皮素-1有反应的羰基化蛋白，包括膜联蛋白 A1。我们的实验提出了一个假设，即内皮素-1 介导的羰基化及其随后的膜联蛋白 A1 降解促进细胞生长。该机制也发生在肺动脉、体循环和气道平滑肌细胞以及心肌细胞对其他信号激活剂（如 5-羟色胺和血小板衍生生长因子）的反应中，提示该途径具有普遍性。我们还发现了脱碳化过程，该过程定义了某些条件下碳酰化信号的瞬时动力学。我们提出，蛋白质的碳酰化和脱碳化是信号转导的一种机制。
