Mass spectrometry imaging for dissecting steroid intracrinology within target tissues.
Mass spectrometry imaging for dissecting steroid intracrinology within target tissues.
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DOI：
10.1021/ac402777k
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发表时间：
2013-12-03
影响因子：
7.4
通讯作者：
Andrew, Ruth
中科院分区：
文献类型：
--
作者：
Cobice, Diego F.;Mackay, C. Logan;Goodwin, Richard J. A.;McBride, Andrew;Langridge-Smith, Patrick R.;Webster, Scott P.;Walker, Brian R.;Andrew, Ruth
组织内的类固醇浓度由细胞内酶调节。这种“类固醇内分泌学”影响依赖性癌症和肥胖症，并提供药理学抑制的靶点。然而，不存在高分辨率的方法来定量靶组织内的类固醇。我们开发了质谱成像（MSI），结合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质谱的组织衍生化，以定量糖皮质激素放大酶11β-HSD 1的底物和产物（11-脱氢皮质酮和皮质酮）。在大鼠肾上腺和小鼠脑切片中以150-200μm分辨率成像局部类固醇分布，并通过碰撞诱导解离/液体提取表面分析进行确认。在11β-HSD 1缺乏或抑制的小鼠脑中，MSI定量了亚区域皮质酮/11-脱氢皮质酮比率、抑制剂分布和替代11β-HSD 1底物7-酮基胆固醇蓄积的变化。MSI数据与全脑匀浆中的LC-MS/MS相关性良好。衍生化MSI是研究组织内类固醇生物学的一种强有力的新工具。
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.
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影响因子：
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作者：
Wake, Deborah J.;Homer, Natalie Z. M.;Walker, Brian R.
通讯作者：
Walker, Brian R.
影响因子：
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Quirke, JME;Van Berkel, GJ
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Van Berkel, GJ
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Griffiths, WJ
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通讯作者：
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作者：
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