Visualizing ATP Dynamics in Live Mice
Visualizing ATP Dynamics in Live Mice
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活体小鼠 ATP 动态可视化
DOI：
10.1101/2020.06.10.143560
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Masamichi Yamamoto
中科院分区：
文献类型：
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作者：
Norimichi Koitabashi; Riki Ogasawara;Ryuto Yasui;Yuki Sugiura;Hinako Matsuda;Shigenori Nonaka;Takashi Izumi;Masahiko Kurabayashi;Makoto Suematsu;Motoko Yanagita;Hiromi Imamura;Masamichi Yamamoto
三磷酸腺苷（ATP）的动力学分析对于定量确定ATP在生物活性中的实际作用至关重要。在这里，我们应用遗传编码的Förster共振能量转移生物传感器“GO-ATeam”，并创建了一个转基因小鼠模型，允许系统ATP水平定量，灵敏，非侵入性，时空测量生理和病理条件下。我们使用该模型在三种不同的条件下容易地进行ATP动力学的活体成像：在运动期间，在所有器官和细胞中;在心肌梗死进展期间;以及响应心脏毒性药物的应用。这些发现提供了令人信服的证据，GO-ATeam小鼠模型是一个强大的工具，以前所未有的时空分辨率实时研究细胞ATPin的多种功能。这将告知预测的分子和形态学响应的扰动ATP水平，以及阐明的生理机制，控制ATP homeostasis.One句子SummaryIntravitial实时成像的ATP动力学在多个器官使用GO-ATeam小鼠，可用于定量，灵敏，非侵入性，和时空测量全身ATP水平，并提供了一个平台，为临床前药理学研究。
Analysis of the dynamics of adenosine triphosphate (ATP) is vital to quantitatively define the actual roles of ATP in biological activities. Here, we applied a genetically encoded Förster resonance energy transfer biosensor “GO-ATeam” and created a transgenic mouse model that allows systemic ATP levels to be quantitatively, sensitively, noninvasively, and spatiotemporally measured under physiological and pathological conditions. We used this model to readily conduct intravital imaging of ATP dynamics under three different conditions: during exercise, in all organs and cells; during myocardial infarction progression; and in response to the application of cardiotoxic drugs. These findings provide compelling evidence that the GO-ATeam mouse model is a powerful tool to investigate the multifarious functions of cellular ATPin vivowith unprecedented spatiotemporal resolution in real-time. This will inform predictions of molecular and morphological responses to perturbations of ATP levels, as well as the elucidation of physiological mechanisms that control ATP homeostasis.One Sentence SummaryIntravital real-time imaging of ATP dynamics in multiple organs using GO-ATeam mice, can be used to quantitatively, sensitively, noninvasively, and spatiotemporally measure systemic ATP levels and provide a platform for preclinical pharmacological studies.