Endoplasmic Reticulum-Targeted Two-Photon Fluorescent Probe for the Detection of Nitroxyl in a Parkinson’s Disease Model,Analytical Chemistry

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Endoplasmic Reticulum-Targeted Two-Photon Fluorescent Probe for the Detection of Nitroxyl in a Parkinson’s Disease Model
Analytical Chemistry ( IF 6.7 ) Pub Date : 2023-04-03 , DOI: 10.1021/acs.analchem.2c05127
Hao Kang ₁ , Wei Shu ₂ , Jin Yu ₁ , Yunpeng Wang ₁ , Xiaoli Zhang ₃ , Rubo Zhang ₁ , Jing Jing ₁ , Xiaoling Zhang _{1,

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Affiliation

Nitroxyl (HNO) and endoplasmic reticulum (ER) stress are considered to play important effects in the administration of many pathological processes of Parkinson’s disease (PD). However, the intricate relationship between the neurotoxicity of HNO and ER stress in the processes of PD is still unknown. To completely comprehend the pathogenic activity of HNO during ER stress and achieve early diagnosis of PD, developing sensitive tools for HNO sensing in vivo is essential. In this work, a two-photon fluorescent probe (KD-HNO) was developed with highly selective and sensitive (7.93 nM) response for HNO in vitro. Then, utilizing KD-HNO, we found that HNO levels were distinctly increased in tunicamycin-stimulated PC12 cells, which are characterized by ER stress and PD features. Most importantly, we detected a considerable increase in HNO levels in the brains of PD-model mice, indicating a positive correlation between PD and HNO levels for the first time. Collectively, these findings revealed that KD-HNO is an excellent tool not only for understanding the biological effects of HNO in pathological processes of PD but also for early PD diagnosis.

中文翻译：

用于检测帕金森氏病模型中硝酰基的内质网靶向双光子荧光探针

硝酰 (HNO) 和内质网 (ER) 压力被认为在帕金森病 (PD) 的许多病理过程的管理中发挥重要作用。然而，HNO 的神经毒性与 PD 过程中 ER 应激之间的复杂关系仍然未知。为了完全了解 ER 应激期间 HNO 的致病活性并实现 PD 的早期诊断，开发用于体内HNO 传感的敏感工具至关重要。在这项工作中，开发了一种双光子荧光探针 ( KD-HNO )，该探针在体外对 HNO 具有高选择性和灵敏 (7.93 nM) 响应。然后，利用KD-HNO, 我们发现 HNO 水平在衣霉素刺激的 PC12 细胞中明显增加, 其特点是 ER 应激和 PD 特征。最重要的是，我们检测到 PD 模型小鼠大脑中 HNO 水平显着增加，这首次表明 PD 和 HNO 水平之间呈正相关。总的来说，这些发现表明，KD-HNO不仅是了解 HNO 在 PD 病理过程中的生物学效应，而且是早期 PD 诊断的极好工具。

更新日期：2023-04-03

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