Cuproptosis accompanied by obvious •OH generation revealed with an ultrasensitive NIR fluorescence probe
Cuproptosis accompanied by obvious •OH generation revealed with an ultrasensitive NIR fluorescence probe
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DOI：
10.1016/j.cej.2023.146749
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发表时间：
2023-11
影响因子：
15.1
通讯作者：
Hongyu Li;Yan An;Xue Luo;Jie Gao;Min Yang;Xinmin Li;Xiaohua Li;Wen Shi;Zeli Yuan;Huimin Ma
中科院分区：
文献类型：
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作者：
Hongyu Li;Yan An;Xue Luo;Jie Gao;Min Yang;Xinmin Li;Xiaohua Li;Wen Shi;Zeli Yuan;Huimin Ma
铜中毒是最近发现的一种铜依赖性调节细胞死亡途径，可能在许多生理和病理过程中发挥作用；然而，铜凋亡过程中活性氧（例如自由基 dotOH 水平）的变化尚不清楚。在此，我们开发了一种用于表征铜凋亡的超灵敏近红外（NIR）荧光探针CDHQ，其揭示了铜凋亡过程中明显的羟基自由基（自由基dotOH）的产生。自由基 dotOH 的特异性氢提取导致 CDHQ 的大 π 共轭延伸和光谱偏移，并伴有高对比度荧光开关响应。 CDHQ 可以检测痕量自由基 dotOH，这是其他方法无法检测到的，例如在没有 H2O2 的情况下低价金属（Fe2+、Ti3+、V3+，尤其是 Cu+）自氧化过程中的电子自旋共振。使用 CDHQ，我们发现在铜凋亡的铜超载细胞中，甚至在细胞死亡之前，就会显着产生自由基 dotOH。此外，CDHQ能够监测活体小鼠中自由基dotOH的产生，因此有望用于研究自由基dotOH在更多生物系统中的体内变化。
Cuproptosis is a recently discovered copper-dependent pathway of regulated cell death, and may play a role in a number of physiological and pathological processes; however, the variation of reactive oxygen species such as radical dotOH level is unclear during cuproptosis. Herein, we have developed an ultrasensitive near-infrared (NIR) fluorescence probe CDHQ for characterizing cuproptosis, which reveals an obvious hydroxyl radical (radical dotOH) generation during cuproptosis. The specific hydrogen abstraction of radical dotOH causes a large π-conjugation extension and spectral shift of CDHQ, accompanied by a high-contrast fluorescence off–on response. CDHQ can detect trace radical dotOH that is undetectable by other methods such as electron spin resonance during autoxidation of low-valent metals (Fe2+, Ti3+, V3+and especially Cu+) in the absence of H2O2. Using CDHQ, we have found that radical dotOH is significantly generated in the copper-overloaded cells of cuproptosis, even before cell death. Moreover, CDHQ is capable of monitoring the generation of radical dotOH in living mice, and thus may be expected to be useful for studying thein vivochange of radical dotOH in more biosystems.