首页> 美国卫生研究院文献>other >Mass Spectrometry Imaging for Dissecting Steroid Intracrinology within Target Tissues
【2h】

Mass Spectrometry Imaging for Dissecting Steroid Intracrinology within Target Tissues

机译:质谱成像解剖目标组织内的类固醇内分泌学

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

Steroid concentrations within tissues are modulated by intracellular enzymes. Such ‘steroid intracrinology’ influences hormone-dependent cancers and obesity, and provides targets for pharmacological inhibition. However, no high resolution methods exist to quantify steroids within target tissues. We developed mass spectrometry imaging (MSI), combining matrix assisted laser desorption ionization with on-tissue derivatization with Girard T and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry, to quantify substrate and product (11-dehydrocorticosterone and corticosterone) of the glucocorticoid-amplifying enzyme 11β-HSD1. Regional steroid distribution was imaged at 150-200μm resolution in rat adrenal gland and mouse brain sections, and confirmed with collision induced dissociation/liquid extraction surface analysis. In brains of mice with 11β-HSD1 deficiency or inhibition, MSI quantified changes in sub-regional corticosterone/11-dehydrocorticosterone ratio, distribution of inhibitor, and accumulation of the alternative 11β-HSD1 substrate, 7-ketocholesterol. MSI data correlated well with LC-MS/MS in whole brain homogenates. MSI with derivatization is a powerful new tool to investigate steroid biology within tissues.
机译:组织内类固醇的浓度受细胞内酶的调节。这种“类固醇内分泌学”影响激素依赖性癌症和肥胖症,并为药理抑制提供靶标。但是,没有高分辨率的方法来量化目标组织中的类固醇。我们开发了质谱成像(MSI),将基质辅助激光解吸电离与吉拉德T和傅立叶变换离子回旋共振共振质谱结合在组织上衍生化,以量化糖皮质激素放大酶的底物和产物(11-脱氢皮质酮和皮质酮) 11β-HSD1。在大鼠肾上腺和小鼠大脑切片中以150-200μm的分辨率对区域类固醇分布进行成像,并通过碰撞诱导的解离/液体萃取表面分析进行了确认。在11β-HSD1缺乏或受抑制的小鼠的大脑中,MSI量化了次区域皮质酮/ 11-脱氢皮质酮之比的变化,抑制剂的分布以及其他11β-HSD1底物7-酮胆固醇的积累。在全脑匀浆中,MSI数据与LC-MS / MS相关性很好。具有衍生功能的MSI是研究组织内类固醇生物学的强大新工具。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号