Mass spectrometry imaging of phosphatidylcholine metabolism in lungs administered with therapeutic surfactants and isotopic tracers.

Mass spectrometry imaging of phosphatidylcholine metabolism in lungs administered with therapeutic surfactants and isotopic tracers.
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用治疗性表面活性剂和同位素示踪剂给药肺中磷脂酰胆碱代谢的质谱成像。

DOI:
10.1016/j.jlr.2021.100023
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发表时间:
2021
影响因子:
6.5
通讯作者:
Postle AD
Postle AD
中科院分区:
生物学2区
文献类型:
--
作者:
Ellis SR;Hall E;Panchal M;Flinders B;Madsen J;Koster G;Heeren RMA;Clark HW;Postle AD

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质谱成像(MSI)可视化整个组织中的分子分布,但对动态代谢过程是盲目的。在这里,MSI与高质量分辨率与多种稳定同位素标记提供了空间分析的磷脂酰胆碱(PC)代谢在小鼠肺。表面活性物质代谢失调是许多呼吸系统疾病的核心。代谢和营业额的治疗肺表面活性剂成像的完整和代谢产物的添加示踪剂,通用13 C-标记的二棕榈酰PC(U13 C-DPPC)的分布。新合成的PC物种的实质分布也从甲基-D9-胆碱的分解成像。这种双重标记策略表明,外源性表面活性剂和作用于U13 C-DPPC标记的表面活性剂的酰基链重塑过程的位置都缺乏对内源性PC合成的抑制,导致形成多不饱和PC脂质。这种可视化离散代谢事件的能力将大大提高我们对不同组织中脂质代谢的理解,并具有潜在的临床和实验研究应用。
Mass spectrometry imaging (MSI) visualizes molecular distributions throughout tissues but is blind to dynamic metabolic processes. Here, MSI with high mass resolution together with multiple stable isotope labeling provided spatial analyses of phosphatidylcholine (PC) metabolism in mouse lungs. Dysregulated surfactant metabolism is central to many respiratory diseases. Metabolism and turnover of therapeutic pulmonary surfactants were imaged from distributions of intact and metabolic products of an added tracer, universally 13C-labeled dipalmitoyl PC (U13C-DPPC). The parenchymal distributions of newly synthesized PC species were also imaged from incorporations of methyl-D9-choline. This dual labeling strategy demonstrated both lack of inhibition of endogenous PC synthesis by exogenous surfactant and location of acyl chain remodeling processes acting on the U13C-DPPC-labeled surfactant, leading to formation of polyunsaturated PC lipids. This ability to visualize discrete metabolic events will greatly enhance our understanding of lipid metabolism in diverse tissues and has potential application to both clinical and experimental studies.
通过质谱法对组织中脂质生物化学的MALDI成像。
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