Dong Baoli, Wang Yan, Wei Hua, Kong Xiuqi, Li Shijing, Yue Tao
School of Chemistry and Chemical Engineering, University of Jinan, Jinan, Shandong, 250022, China.
Shandong Chemical Technology Academy, Qingdao University of Science and Technology (Jinan), Jinan, Shandong, 250014, China.
Anal Chim Acta. 2023 Sep 22;1275:341571. doi: 10.1016/j.aca.2023.341571. Epub 2023 Jun 28.
Ferroptosis is a novel Fe(II)-mediated oxidative cell death form, and is closely related with endoplasmic reticulum (ER). Exploring the fluctuation of ER polarity during ferroptosis is highly important for the in-depth study of the biological roles of ER in ferroptosis. Herein, we present a ratiometric probe (BNS) for revealing the changes of the ER polarity in the living cells experiencing ferroptosis. BNS employed a D-π-A-π-D type structure as the polarity-sensitive fluorophore, and selected p-toluenesulfonamide as the ER-targeting unit. Theoretical calculations suggested that the response mechanism of BNS to polarity was based on ICT, and two ICT processes appeared when BNS was at excited state. Cell imaging results demonstrated that BNS possessed desirable ER-targeting capability, and erastin-induced ferroptosis could increase the ER polarity of the living cells. Moreover, similarly to vitamin E (VE) and deferoxamine (DFO), dihydrolipoic acid (DHLA) could inhibit the changes of the ER polarity during erastin-induced ferroptosis. We expect that the probe could provide a convenient method to rapidly monitor ferroptosis and design novel drugs for the treatment of ferroptosis-relevant diseases.
铁死亡是一种新型的铁（II）介导的氧化性细胞死亡形式，与内质网（ER）密切相关。探索铁死亡过程中内质网极性的波动对于深入研究内质网在铁死亡中的生物学作用至关重要。在此，我们提出了一种比率型探针（BNS），用于揭示经历铁死亡的活细胞中内质网极性的变化。BNS采用D-π-A-π-D型结构作为极性敏感荧光团，并选择对甲苯磺酰胺作为内质网靶向单元。理论计算表明，BNS对极性的响应机制基于分子内电荷转移（ICT），且BNS处于激发态时会出现两个ICT过程。细胞成像结果表明，BNS具有理想的内质网靶向能力，且erastin诱导的铁死亡可增加活细胞的内质网极性。此外，与维生素E（VE）和去铁胺（DFO）类似，二氢硫辛酸（DHLA）可抑制erastin诱导的铁死亡过程中内质网极性的变化。我们期望该探针能够提供一种便捷的方法来快速监测铁死亡，并设计用于治疗铁死亡相关疾病的新型药物。
