School of Chemistry and Chemical Engineering, University of Jinan, Jinan, Shandong 250022, China.
Shandong Anshun Pharmaceutical Company, Limited, Laoling, Shandong 253600, China.
Anal Chem. 2024 Apr 16;96(15):5992-6000. doi: 10.1021/acs.analchem.4c00328. Epub 2024 Apr 4.
Hypochlorous acid (HClO) is a typical endogenous ROS produced mainly in mitochondria, and it has strong oxidative properties. Abnormal HClO levels lead to mitochondrial dysfunction, strongly associated with various diseases. It has been shown that HClO shows traces of overexpression in cells of both ferroptosis and hepatocellular carcinoma (HCC). Therefore, visualization of HClO levels during ferroptosis of HCC is important to explore its physiological and pathological roles. So far, there has been no report on the visualization of HClO in ferroptosis of HCC. Thus, we present a ratiometric near-infrared (NIR) fluorescent probe which visualized for the first time the fluctuation of HClO in mitochondria during ferroptosis of HCC. has an ultrafast response rate (2 s) and large emission shift (115 nm). was constructed based on the PET sensing mechanism and thus has a high signal-to-noise ratio. The cell experiments of demonstrated that Fe- and erastin-induced ferroptosis in HepG2 cells resulted in elevated levels of mitochondrial HClO and that high concentration levels of Fe and erastin cause severe mitochondrial damage and oxidative stress and had the potential to kill HepG2 cells. By regulating the erastin concentration, erastin induction time, and treatment of the ferroptosis model, can accurately detect the fluctuation of mitochondrial HClO levels during ferroptosis in HCC.
次氯酸（HClO）是一种典型的内源性 ROS，主要在线粒体中产生，具有很强的氧化性质。异常的 HClO 水平导致线粒体功能障碍，与各种疾病密切相关。已经表明，在铁死亡和肝癌（HCC）细胞中，HClO 表现出微量过表达。因此，在 HCC 的铁死亡过程中可视化 HClO 水平对于探索其生理和病理作用非常重要。到目前为止，还没有关于 HCC 铁死亡中 HClO 可视化的报道。因此，我们提出了一种比率型近红外（NIR）荧光探针 ，该探针首次可视化了 HCC 铁死亡过程中线粒体中 HClO 的波动。 具有超快的响应速率（2 s）和大的发射位移（115 nm）。 基于 PET 传感机制构建，因此具有高信噪比。 的细胞实验表明，Fe 和 erastin 诱导的 HepG2 细胞铁死亡导致线粒体 HClO 水平升高，而高浓度的 Fe 和 erastin 导致严重的线粒体损伤和氧化应激，并有潜在杀死 HepG2 细胞的能力。通过调节 erastin 浓度、erastin 诱导时间和铁死亡模型的处理， 可以准确检测 HCC 中铁死亡过程中线粒体 HClO 水平的波动。
