Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, 02139, USA.
Nat Commun. 2018 Aug 7;9(1):3145. doi: 10.1038/s41467-018-05557-y.
Redox cancer therapeutics target the increased reliance on intracellular antioxidant systems and enhanced susceptibility to oxidant-induced stress of some cancer cells compared to normal cells. Many of these therapeutics are thought to perturb intracellular levels of the oxidant hydrogen peroxide (HO), a signaling molecule that modulates a number of different processes in human cells. However, fluorescent probes for this species remain limited in their ability to detect the small perturbations induced during successful treatments. We report a fluorescent sensor based upon human peroxiredoxin-2, which acts as the natural indicator of small HO fluctuations in human cells. The new probe reveals peroxide-induced oxidation in human cells below the detection limit of current probes, as well as peroxiredoxin-2 oxidation caused by two different redox cancer therapeutics in living cells. This capability will be useful in elucidating the mechanism of current redox-based therapeutics and in developing new ones.
氧化还原癌症治疗针对的是某些癌细胞与正常细胞相比，对细胞内抗氧化系统的依赖增加和对氧化剂诱导的应激的敏感性增强。许多这些治疗剂被认为会扰乱细胞内氧化剂过氧化氢 (HO) 的水平，HO 是一种信号分子，调节人类细胞中的许多不同过程。然而，用于该物质的荧光探针在检测成功治疗期间诱导的小扰动方面仍然存在局限性。我们报告了一种基于人过氧化物酶-2 的荧光传感器，它可作为人细胞中 HO 小波动的天然指示剂。新的探针揭示了低于当前探针检测限的人细胞中过氧化物诱导的氧化，以及两种不同的氧化还原癌症治疗剂在活细胞中引起的过氧化物酶-2 氧化。这种能力将有助于阐明当前基于氧化还原的治疗剂的机制，并开发新的治疗剂。
Zotero 插件
