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Anatomical-Molecular Distribution of EphrinA1 in Infarcted Mouse Heart Using MALDI Mass Spectrometry Imaging
Journal of the American Society for Mass Spectrometry ( IF 3.2 ) Pub Date : 2018-01-05 , DOI: 10.1007/s13361-017-1869-7
Stephan Lefcoski 1 , Kimberly Kew 2 , Shaun Reece 1 , Maria J. Torres 3 , Justin Parks 1 , Sky Reece 1 , Lisandra E. de Castro Brás 1 , Jitka A. I. Virag 1
Affiliation  

EphrinA1 is a tyrosine kinase receptor localized in the cellular membrane of healthy cardiomyocytes, the expression of which is lost upon myocardial infarction (MI). Intra-cardiac injection of the recombinant form of ephrinA1 (ephrinA1-Fc) at the time of ligation in mice has shown beneficial effects by reducing infarct size and myocardial necrosis post-MI. To date, immunohistochemistry and Western blotting comprise the only experimental approaches utilized to localize and quantify relative changes of ephrinA1 in sections and homogenates of whole left ventricle, respectively. Herein, we used matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) coupled with a time-of-flight mass spectrometer (MALDI/TOF MS) to identify intact as well as tryptic fragments of ephrinA1 in healthy controls and acutely infarcted murine hearts. The purpose of the present study was 3-fold: (1) to spatially resolve the molecular distribution of endogenous ephrinA1, (2) to determine the anatomical expression profile of endogenous ephrinA1 after acute MI, and (3) to identify molecular targets of ephrinA1-Fc action post-MI. The tryptic fragments detected were identified as the ephrinA1-isoform with 38% and 34% sequence coverage and Mascot scores of 25 for the control and MI hearts, respectively. By using MALDI-MSI, we have been able to simultaneously measure the distribution and spatial localization of ephrinA1, as well as additional cardiac proteins, thus offering valuable information for the elucidation of molecular partners, mediators, and targets of ephrinA1 action in cardiac muscle.

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中文翻译:

MALDI质谱成像分析梗死小鼠心脏中EphrinA1的解剖-分子分布

EphrinA1是一种位于健康心肌细胞膜中的酪氨酸激酶受体,其表达在心肌梗塞(MI)后消失。在小鼠结扎时心内注射ephrinA1的重组形式(ephrinA1-Fc)已显示出减少MI后梗死面积和心肌坏死的有益作用。迄今为止,免疫组织化学和蛋白质印迹法是唯一用于分别定位和定量整个左心室切片和匀浆中ephrinA1相对变化的实验方法。在本文中,我们使用基质辅助激光解吸电离质谱成像(MALDI-MSI)结合飞行时间质谱仪(MALDI / TOF MS)来鉴定健康对照和急性梗塞的ephrinA1的完整和胰蛋白酶碎片鼠心。本研究的目的是3倍:(1)在空间上解析内源性ephrinA1的分子分布,(2)确定急性MI后内源性ephrinA1的解剖表达谱,以及(3)识别ephrinA1的分子靶标-Fc作用于MI后。所检测到的胰蛋白酶片段被鉴定为ephrinA1同工型,对照和MI心脏的序列覆盖率分别为38%和34%,Mascot得分分别为25。通过使用MALDI-MSI,我们能够同时测量ephrinA1以及其他心脏蛋白的分布和空间定位,从而为阐明心肌中ephrinA1作用的分子伴侣,介体和靶标提供了有价值的信息。(1)在空间上解析内源性ephrinA1的分子分布,(2)确定急性MI后内源性ephrinA1的解剖表达谱,以及(3)识别MI后的ephrinA1-Fc作用的分子靶标。所检测到的胰蛋白酶片段被鉴定为ephrinA1同工型,对照和MI心脏的序列覆盖率分别为38%和34%,Mascot得分分别为25。通过使用MALDI-MSI,我们能够同时测量ephrinA1以及其他心脏蛋白的分布和空间定位,从而为阐明心肌中ephrinA1作用的分子伴侣,介体和靶标提供了有价值的信息。(1)在空间上解析内源性ephrinA1的分子分布,(2)确定急性MI后内源性ephrinA1的解剖表达谱,以及(3)识别MI后的ephrinA1-Fc作用的分子靶标。所检测到的胰蛋白酶片段被鉴定为ephrinA1同工型,对照和MI心脏的序列覆盖率分别为38%和34%,Mascot得分分别为25。通过使用MALDI-MSI,我们能够同时测量ephrinA1以及其他心脏蛋白的分布和空间定位,从而为阐明心肌中ephrinA1作用的分子伴侣,介体和靶标提供了有价值的信息。(3)确定MI后ephrinA1-Fc作用的分子靶标。所检测到的胰蛋白酶片段被鉴定为ephrinA1同工型,对照和MI心脏的序列覆盖率分别为38%和34%,Mascot得分分别为25。通过使用MALDI-MSI,我们能够同时测量ephrinA1以及其他心脏蛋白的分布和空间定位,从而为阐明心肌中ephrinA1作用的分子伴侣,介体和靶标提供了有价值的信息。(3)确定MI后ephrinA1-Fc作用的分子靶标。所检测到的胰蛋白酶片段被鉴定为ephrinA1同工型,对照和MI心脏的序列覆盖率分别为38%和34%,Mascot得分分别为25。通过使用MALDI-MSI,我们能够同时测量ephrinA1以及其他心脏蛋白的分布和空间定位,从而为阐明心肌中ephrinA1作用的分子伴侣,介体和靶标提供了有价值的信息。

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更新日期:2018-01-05
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