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首页> 外文期刊>American Journal of Physiology >Mass spectrometry for the molecular imaging of angiotensin metabolism in kidney
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Mass spectrometry for the molecular imaging of angiotensin metabolism in kidney

机译：质谱用于肾脏中血管紧张素代谢的分子成像

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摘要

To better understand the tissue distribution and activity of enzymes involved in angiotensin II (Ang II) processing, we developed a novel molecular imaging method using matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. Mouse kidney sections (12 m) were incubated with 10-1,000 mol/l Ang II for 5-15 min at 37??C. The formed peptides Ang III and Ang-(1-7) were identified by MALDI-TOF/TOF. A third metabolite, Ang-(1-4), was generated from further degradation of Ang-(1-7). Enzymatic processing of Ang II was dose and time dependent and absent in heat-treated kidney sections. Distinct spatial distribution patterns (pseudocolor images) were observed for the peptides. Ang III was localized in renal medulla, whereas Ang-(1-7)/Ang-(1-4) was present in cortex. Regional specific peptide formation was confirmed using microdissected cortical and medullary biopsies. In vitro studies with recombinant enzymes confirmed activity of peptidases known to generate Ang III or Ang-(1-7) from Ang II: aminopeptidase A (APA), Ang-converting enzyme 2 (ACE2), prolyl carboxypeptidase (PCP), and prolyl endopeptidase (PEP). Renal medullary Ang III generation was blocked by APA inhibitor glutamate phosphonate. The ACE2 inhibitor MLN-4760 and PCP/PEP inhibitor Z-pro-prolinal reduced cortical Ang-(1-7) formation. Our results establish the power of MALDI imaging as a highly specific and information-rich analytical technique that will further aid our understanding of the role and site of Ang II processing in cardiovascular and renal pathologies. ? 2012 the American Physiological Society.
机译：为了更好地了解血管紧张素II（Ang II）处理中涉及的酶的组织分布和活性，我们开发了一种使用基质辅助激光解吸电离飞行时间（MALDI-TOF）质谱的新型分子成像方法。将小鼠肾脏切片（12 m）与10-1,000 mol / l Ang II在37°C下孵育5-15分钟。通过MALDI-TOF / TOF鉴定形成的肽Ang III和Ang-（1-7）。 Ang-（1-7）的进一步降解产生了第三种代谢产物Ang-（1-4）。 Ang II的酶处理取决于剂量和时间，在热处理的肾脏切片中不存在。观察到了肽的不同的空间分布模式（伪彩色图像）。 Ang III位于肾髓质中，而Ang-（1-7）/ Ang-（1-4）存在于皮质中。使用显微解剖的皮质和髓样活检证实了区域特异性肽的形成。用重组酶进行的体外研究证实了已知可从Ang II产生Ang III或Ang-（1-7）的肽酶的活性：氨基肽酶A（APA），Ang转化酶2（ACE2），脯氨酰羧肽酶（PCP）和脯氨酰内肽酶（PEP）。肾髓质血管紧张素Ⅲ的生成被APA抑制剂谷氨酸膦酸酯所阻断。 ACE2抑制剂MLN-4760和PCP / PEP抑制剂Z-pro-proalal减少了皮质Ang-（1-7）的形成。我们的结果确立了MALDI成像作为一种高度特异性和信息丰富的分析技术的力量，这将进一步帮助我们了解Ang II加工在心血管和肾脏病理中的作用和部位。 ？ 2012年美国生理学会。

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