A universal fluorogenic switch for Fe(ii) ion based on N-oxide chemistry permits the visualization of intracellular redox equilibrium shift towards labile iron in hypoxic tumor cells.
A universal fluorogenic switch for Fe(ii) ion based on N-oxide chemistry permits the visualization of intracellular redox equilibrium shift towards labile iron in hypoxic tumor cells.
复制标题
DOI：
10.1039/c6sc05457a
复制
发表时间：
2017-07-01
期刊：
影响因子：
8.4
通讯作者：
Nagasawa H
中科院分区：
文献类型：
--
作者：
Hirayama T;Tsuboi H;Niwa M;Miki A;Kadota S;Ikeshita Y;Okuda K;Nagasawa H
利用一种新型n-氧化物基荧光探针观察了不稳定Fe（ii）离子的氧依赖性波动。铁（Fe）物种在生物学和病理学上起着重要的作用。特别是，铁是活组织中氧传感的关键元素，其代谢与氧代谢密切相关。调节不稳定铁的氧化还原平衡以防止铁催化的活性氧（ROS）的产生对生存至关重要。然而，由于缺乏铁，特别是不稳定的Fe2+的氧化还原状态特异性检测方法，对铁物种氧化还原稳态的研究具有挑战性。本研究建立了一种通用荧光开关系统，该系统基于独特的n -氧化物化学特性，对Fe2+离子有响应，其中二烷基基胺n -氧化物被Fe2+选择性脱氧，生成Fe2+ -CoNox-1（蓝色）、FluNox-1（绿色）和SiRhoNox-1（红色）等多种荧光探针。所有探针在试管和活细胞中对Fe2+都表现出高选择性的荧光增强。在这些探针中，SiRhoNox-1在反应速率和开关信号对比度方面都表现出良好的荧光响应。利用SiRhoNox-1进行的成像研究显示，活细胞和三维肿瘤球体中氧张力降低时，细胞内氧化还原平衡向不稳定铁转移，并发现缺氧诱导不稳定铁的产生不依赖于铁摄取、缺氧诱导的信号传导和缺氧激活的酶。本研究证明了开发具有精细光物理特性的Fe2+敏感和特异性荧光探针的可行性，使其能够广泛应用于各种生理和病理条件下的铁研究。
Oxygen-dependent fluctuation of labile Fe(ii) was visualized by a new N-oxide-based fluorescent probe for Fe(ii) ion. Iron (Fe) species play a number of biologically and pathologically important roles. In particular, iron is a key element in oxygen sensing in living tissue where its metabolism is intimately linked with oxygen metabolism. Regulation of redox balance of labile iron species to prevent the generation of iron-catalyzed reactive oxygen species (ROS) is critical to survival. However, studies on the redox homeostasis of iron species are challenging because of a lack of a redox-state-specific detection method for iron, in particular, labile Fe2+. In this study, a universal fluorogenic switching system is established, which is responsive to Fe2+ ion based on a unique N-oxide chemistry in which dialkylarylamine N-oxide is selectively deoxygenized by Fe2+ to generate various fluorescent probes of Fe2+–CoNox-1 (blue), FluNox-1 (green), and SiRhoNox-1 (red). All the probes exhibited fluorescence enhancement against Fe2+ with high selectivity both in cuvette and in living cells. Among the probes, SiRhoNox-1 showed an excellent fluorescence response with respect to both reaction rate and off/on signal contrast. Imaging studies were performed showing the intracellular redox equilibrium shift towards labile iron in response to reduced oxygen tension in living cells and 3D tumor spheroids using SiRhoNox-1, and it was found that the hypoxia induction of labile Fe2+ is independent of iron uptake, hypoxia-induced signaling, and hypoxia-activated enzymes. The present studies demonstrate the feasibility of developing sensitive and specific fluorescent probes for Fe2+ with refined photophysical characteristics that enable their broad application in the study of iron in various physiological and pathological conditions.
登录
查看更多内容
影响因子：
4
作者：
Hider, Robert C.;Kong, Xiaole
通讯作者：
Kong, Xiaole
影响因子：
5.8
作者：
Haddad JJ
通讯作者：
Haddad JJ
影响因子：
3.7
作者：
Gomes A;Guillaume L;Grimes DR;Fehrenbach J;Lobjois V;Ducommun B
通讯作者：
Ducommun B
影响因子：
3.9
作者：
Crichton, RR;Wilmet, S;Ward, RJ
通讯作者：
Ward, RJ
影响因子：
8.4
作者：
Hirayama, Tasuku;Okuda, Kensuke;Nagasawa, Hideko
通讯作者：
Nagasawa, Hideko