Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Department of Pharmacy and Pharmacology, Hengyang Medical School, University of South China, Hengyang, 421002, China.
Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Department of Pharmacy and Pharmacology, Hengyang Medical School, University of South China, Hengyang, 421002, China.
Talanta. 2024 Nov 1;279:126635. doi: 10.1016/j.talanta.2024.126635. Epub 2024 Jul 30.
Heightened oxidative stress is the principal driver behind the altered metabolism of neurotransmitters within the brains of Parkinson's disease (PD). Hypochlorous acid (HClO), a variant of reactive oxygen species (ROS), plays a crucial role in several lysosomal activities. An irregular concentration of HClO may result in significant molecular damage and contribute to the onset of neurodegenerative disorders. Despite this, the precise role of lysosomal HClO in PD remains unclear, due to its fast reactivity and low levels. This is further complicated by the lack of effective in situ imaging techniques for accurately tracking its dynamics. Therefore, it is of great significance to use effective tools to map the lysosomal HClO during the pathological process of PD. In this study, we propose a fluorogenic probe named Lys-PTZ-HClO for the specific and sensitive detection of HClO. Lys-PTZ-HClO exhibits features like a fast response time (10 s) and a low detection limit (0.72 μM). Benefiting from its superior properties, the probe was used to visualize the basal HClO levels, and the variation of HClO levels in lysosomal of living cells. More importantly, this probe was successfully applied for the first time to reveal increased lysosomal HClO in a cellular model of PD.
氧化应激增强是帕金森病 (PD) 患者大脑中神经递质代谢改变的主要驱动因素。次氯酸 (HClO) 作为活性氧 (ROS) 的一种变体，在几种溶酶体活性中发挥着关键作用。HClO 浓度异常可能导致显著的分子损伤，并导致神经退行性疾病的发生。尽管如此，由于其快速反应性和低水平，溶酶体 HClO 在 PD 中的确切作用仍不清楚。这进一步因缺乏用于准确跟踪其动力学的有效原位成像技术而变得复杂。因此，使用有效的工具来绘制 PD 病理过程中的溶酶体 HClO 具有重要意义。在这项研究中，我们提出了一种名为 Lys-PTZ-HClO 的荧光探针，用于 HClO 的特异性和灵敏检测。Lys-PTZ-HClO 具有快速响应时间 (10 s) 和低检测限 (0.72 μM) 的特点。得益于其优越的性能，该探针被用于可视化活细胞中溶酶体的基础 HClO 水平和 HClO 水平的变化。更重要的是，该探针首次成功应用于揭示 PD 细胞模型中溶酶体 HClO 的增加。
