Non-invasive imaging of the levels and effects of glutathione on the redox status of mouse brain using electron paramagnetic resonance imaging
Non-invasive imaging of the levels and effects of glutathione on the redox status of mouse brain using electron paramagnetic resonance imaging
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DOI：
10.1016/j.bbrc.2017.02.134
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发表时间：
2017-04-15
影响因子：
3.1
通讯作者：
Fujii, Hirotada G.
中科院分区：
文献类型：
--
作者：
Emoto, Miho C.;Matsuoka, Yuta;Fujii, Hirotada G.
谷胱甘肽（GSH）是最丰富的非蛋白巯基，缓冲大脑中的活性氧。GSH不直接还原氮氧自由基，但在抗坏血酸存在下，GSH的加入增加了抗坏血酸诱导的氮氧自由基还原。在这项研究中，我们使用电子顺磁共振（EPR）成像和氮氧化物成像探针，3-甲氧羰基-2，2，5，5-四甲基-哌啶-1-氧基（MCP），非侵入性地获得空间分辨的氧化还原数据，从小鼠脑谷胱甘肽耗尽与马来酸二乙酯相比，控制。基于MCP在小鼠头部还原反应的药代动力学，计算其基于像素的还原反应速率常数作为体内氧化还原状态的指标，并绘制成“氧化还原图”。从对照组和GSH耗竭小鼠脑中获得的氧化还原图谱显示脑氧化还原状态的明显变化，这是由于通过生化测定测量的脑中GSH水平降低所致。我们观察到MCP的还原速率常数和GSH水平之间的线性关系，无论是控制和GSH耗尽小鼠大脑。利用这种关系，脑中的GSH水平可以从EPR成像获得的氧化还原图中估计。(C)2017爱思唯尔公司All rights reserved.
Glutathione (GSH) is the most abundant non-protein thiol that buffers reactive oxygen species in the brain. GSH does not reduce nitroxides directly, but in the presence of ascorbates, addition of GSH increases ascorbate-induced reduction of nitroxides. In this study, we used electron paramagnetic resonance (EPR) imaging and the nitroxide imaging probe, 3-methoxycarbonyl-2,2,5,5-tetramethyl-piperidine-1-oxyl (MCP), to non-invasively obtain spatially resolved redox data from mouse brains depleted of GSH with diethyl maleate compared to control. Based on the pharmacokinetics of the reduction reaction of MCP in the mouse heads, the pixel-based rate constant of its reduction reaction was calculated as an index of the redox status in vivo and mapped as a "redox map". The obtained redox maps from control and GSH-depleted mouse brains showed a clear change in the brain redox status, which was due to the decreased levels of GSH in brains as measured by a biochemical assay. We observed a linear relationship between the reduction rate constant of MCP and the level of GSH for both control and GSH-depleted mouse brains. Using this relationship, the GSH level in the brain can be estimated from the redox map obtained with EPR imaging. (C) 2017 Elsevier Inc. All rights reserved.