Mitochondria-Targeted DNA Nanoprobe for Real-Time Imaging and Simultaneous Quantification of Ca2+ and pH in Neurons
Mitochondria-Targeted DNA Nanoprobe for Real-Time Imaging and Simultaneous Quantification of Ca2+ and pH in Neurons
复制标题
线粒体靶向 DNA 纳米探针，用于神经元中 Ca2 和 pH 的实时成像和同步定量
DOI：
10.1021/acsnano.8b06322
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发表时间：
2018-12-01
期刊：
影响因子：
17.1
通讯作者：
Tian, Yang
中科院分区：
文献类型：
--
作者：
Liu, Zhichao;Pei, Hao;Tian, Yang
在此，设计并创建了一种高选择性的DNA纳米探针，用于使用Ca 2+和pH对两种生物物种进行实时成像和同时定量;选择分子作为模型是因为它们与细胞功能和疾病密切相关。合成了一种Ca 2+荧光探针，并将其与pH响应性、内参照和靶向分子一起组装到DNA纳米结构上。这种具有高空间分辨率的纳米探针，以及长期的荧光和结构稳定性，在线粒体中的相同位置处有力地跟踪pH和Ca 2+动态，以响应O-2（中心点）诱导的氧化应激和聚集的淀粉样蛋白β（A β）刺激，时间分辨率为毫秒。使用这个工具，我们发现O-2（中心点-）和A β触发短暂的细胞质酸中毒，然后激活线粒体膜中的酸敏感离子通道la（ASIC 1a），导致线粒体Ca 2+过载和pH异常，这有助于神经元死亡。此外，psalmotoxin 1有效地保护免受O-2（中心点-）-和A β诱导的神经元损伤。
Herein, a single highly selective DNA nanoprobe was designed and created for the real-time imaging and simultaneous quantification of two kinds of biological species using Ca2+ and pH; the molecules were selected as models because of their close relationship with cellular functions and diseases. A Ca2+ fluorescent probe was synthesized and assembled onto a DNA nanostructure together with pH-responsive, inner-reference, and mitochondria-targeted molecules. This nanoprobe with high spatial resolution, together with long-term fluorescent and structural stability, powerfully tracked pH and Ca2+ dynamics at the same localization in mitochondria in response to O-2(center dot-)-induced oxidative stress and aggregated amyloid beta (A beta) stimulation with a temporal resolution of milliseconds. Using this tool, we discovered that O-2(center dot-) and A beta triggered transitory cytoplasmic acidosis and then activated acid-sensing ion channel la (ASIC1a) in the mitochondrial membrane, leading to mitochondrial Ca2+ overload and pH abnormalities, which contribute to neuron death. Moreover, psalmotoxin 1 effectively protected against O-2(center dot-) - and A beta-induced neuron injury.