Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02215, USA; Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon, 34134, South Korea.
Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.
Biosens Bioelectron. 2021 Apr 15;178:113031. doi: 10.1016/j.bios.2021.113031. Epub 2021 Jan 29.
Aberrant production of reactive oxygen species (ROS) leads to tissue damage accumulation, which is associated with a myriad of human pathologies. Although several sensors have been developed for ROS quantification, their applications for ROS-related human physiologies and pathologies still remain problematic due to the unstable nature of ROS. Herein, we developed Trx1-cpYFP-fRMsr (TYfR), a genetically-encoded fluorescent biosensor with the remarkable specificity and sensitivity toward fMetRO (free Methionine-R-sulfoxide), allowing for dynamic quantification of physiological levels of fMetRO, a novel indicator of ROS and methionine redox status in vitro and in vivo. Moreover, using the sensor, we observed a significant fMetRO enrichment in serum from patients with acute coronary syndrome, one of the most severe cardiovascular diseases, which becomes more evident following percutaneous coronary intervention. Collectively, this study proposes that fMetRO is a novel biomarker of tissue damage accumulation in ROS-associated human pathologies, and that TYfR is a promising tool for quantifying fMetRO with potentials in versatile applications.
活性氧（ROS）的异常产生导致组织损伤的积累，这与许多人类疾病有关。尽管已经开发出几种用于 ROS 定量的传感器，但由于 ROS 的不稳定性，它们在 ROS 相关的人类生理学和病理学中的应用仍然存在问题。在这里，我们开发了 Trx1-cpYFP-fRMsr（TYfR），这是一种基因编码的荧光生物传感器，对 fMetRO（游离甲硫氨酸-R-亚砜）具有显著的特异性和敏感性，可动态定量生理水平的 fMetRO，这是一种新的 ROS 和甲硫氨酸氧化还原状态的体外和体内标志物。此外，使用该传感器，我们观察到急性冠状动脉综合征（一种最严重的心血管疾病）患者血清中的 fMetRO 明显富集，经皮冠状动脉介入治疗后更为明显。总的来说，这项研究表明 fMetRO 是 ROS 相关人类疾病中组织损伤积累的一种新型生物标志物，TYfR 是一种有前途的定量检测 fMetRO 的工具，具有多种应用潜力。
