UK Dementia Research Institute at King's College London, London, SE5 9RT, United Kingdom.
The Wohl Institute at King's College London, London, SE5 9RT, United Kingdom.
Sci Rep. 2019 Dec 17;9(1):19282. doi: 10.1038/s41598-019-55799-z.
Understanding the cell response to oxidative stress in disease is an important but difficult task. Here, we demonstrate the feasibility of using a nanomotion sensor to study the cellular metabolic landscape. This nanosensor permits the non-invasive real-time detection at the single-cell level and offers high sensitivity and time resolution. We optimised the technique to study the effects of frataxin overexpression in a cellular model of Friedreich's ataxia, a neurodegenerative disease caused by partial silencing of the FXN gene. Previous studies had demonstrated that FXN overexpression are as toxic as silencing, thus indicating the importance of a tight regulation of the frataxin levels. We probed the effects of frataxin overexpression in the presence of oxidative stress insults and measured the metabolic response by the nanosensor. We show that the nanosensor provides new detailed information on the metabolic state of the cell as a function of time, that agrees with and complements data obtained by more traditional techniques. We propose that the nanosensor can be used in the future as a new and powerful tool to study directly how drugs modulate the effects of oxidative stress on Friedreich's ataxia patients and, more in general, on other neurodegenerative processes.
了解疾病中细胞对氧化应激的反应是一项重要但具有挑战性的任务。在这里,我们展示了使用纳米运动传感器研究细胞代谢图谱的可行性。这种纳米传感器可以在单细胞水平上进行非侵入性的实时检测,具有高灵敏度和时间分辨率。我们优化了该技术,以研究弗里德里希共济失调症(一种由 FXN 基因部分沉默引起的神经退行性疾病)的细胞模型中 frataxin 过表达的影响。先前的研究表明,FXN 过表达与沉默一样具有毒性,这表明 frataxin 水平的严格调控非常重要。我们在存在氧化应激损伤的情况下探测了 frataxin 过表达的影响,并通过纳米传感器测量了代谢反应。我们表明,纳米传感器可以提供有关细胞代谢状态的新的详细信息,这些信息随时间变化,与更传统技术获得的数据一致且互补。我们提出,纳米传感器将来可以作为一种新的强大工具,直接研究药物如何调节氧化应激对弗里德里希共济失调症患者的影响,更普遍地说,还可以研究其他神经退行性过程。