Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Boston, Massachusetts, USA, 02129.
Department of Radiology and Imaging Sciences, Emory University, Atlanta, Georgia, 30322, United States.
Angew Chem Int Ed Engl. 2024 Oct 1;63(40):e202409896. doi: 10.1002/anie.202409896. Epub 2024 Sep 2.
Numerous methods have been reported for detecting ROS/RNS in vitro and in vivo; however, detecting methods for the secondary products of the reactive oxygen species (ROS)/reactive nitrogen species (RNS) reactions, particularly quasi-stable oxidized products, have been much less explored. In this report, we observed that half-curcumins could generate chemiluminescence (CL). In contrast to other chemiluminescence scaffolds, the distinguishing feature of a half-curcumin is the formation of a carbanion intermediate of its acetylacetone moiety, opening unique avenues for applications. In this study, we designed a series of half-curcumins CRANAD-Xs and found that CRANAD-164 could be used to detect quasi-stable oxidized proteins (QSOP) in vivo and in patient serum samples. We illustrated that CRANAD-164 could be used to monitor the responses of taurine, an amino acid with newly reported anti-aging capacity, in an inflammatory mouse model. Remarkably, we further demonstrated that the QSOP levels were much higher in the disease serum samples, including Alzheimer's disease (AD), compared to the samples from healthy controls. Moreover, our results revealed that the sera chemiluminescence intensities were higher in aged healthy controls compared to young healthy subjects, suggesting that CRANAD-164 can be used to monitor the increase of QSOP during aging.
已经有许多方法被报道用于检测 ROS/RNS 在体外和体内;然而,对于活性氧(ROS)/活性氮(RNS)反应的次级产物的检测方法,特别是准稳定的氧化产物的检测方法,探索得要少得多。在本报告中,我们观察到半姜黄素可以产生化学发光(CL)。与其他化学发光支架不同,半姜黄素的一个特点是其乙酰丙酮部分形成碳负离子中间体,为应用开辟了独特的途径。在这项研究中,我们设计了一系列的半姜黄素 CRANAD-Xs,并发现 CRANAD-164 可以用于体内和患者血清样本中检测准稳定氧化蛋白(QSOP)。我们说明了 CRANAD-164 可以用于监测牛磺酸的反应,牛磺酸是一种具有新报道的抗衰老能力的氨基酸,在炎症小鼠模型中。值得注意的是,我们进一步证明,与来自健康对照者的样本相比,疾病血清样本中的 QSOP 水平要高得多,包括阿尔茨海默病(AD)。此外,我们的结果表明,与年轻的健康受试者相比,年龄较大的健康对照者的血清化学发光强度更高,这表明 CRANAD-164 可以用于监测衰老过程中 QSOP 的增加。