使用超高效液相色谱-串联质谱法评估外源药物改变的胆固醇稳态

Josi Herron, Kelly M. Hines, Libin Xu
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引用次数: 11

摘要

胆固醇和胆固醇衍生的氧甾醇对胚胎发育、突触形成和功能、髓鞘形成以及其他生物功能至关重要。事实上,胆固醇、甾醇前体和氧化甾醇水平的改变会导致各种发育障碍,这就强调了胆固醇稳态的重要性。外源药物通过改变胆固醇稳态来复制相似表型的能力越来越引起人们的兴趣。因此,定量评估暴露于外源性药物引起的胆固醇稳态改变的能力是有价值的。本单元描述了使用超高高效液相色谱-串联质谱(UHPLC-MS/MS)对各种样品类型中改变后的角鲨烯胆固醇生物合成和随后的氧化固醇形成进行定量评估的方法。了解由外源暴露引起的胆固醇稳态的改变可以为毒物的作用机制和导致的表型提供关键的见解。©2018 by John Wiley &儿子,Inc。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Assessment of Altered Cholesterol Homeostasis by Xenobiotics Using Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry

Assessment of Altered Cholesterol Homeostasis by Xenobiotics Using Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry

Assessment of Altered Cholesterol Homeostasis by Xenobiotics Using Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry

Assessment of Altered Cholesterol Homeostasis by Xenobiotics Using Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry

Cholesterol and cholesterol-derived oxysterols are critical for embryonic development, synapse formation and function, and myelination, among other biological functions. Indeed, alterations in levels of cholesterol, sterol precursors, and oxysterols result in a variety of developmental disorders, emphasizing the importance of cholesterol homeostasis. The ability of xenobiotics to reproduce similar phenotypes by altering cholesterol homeostasis has increasingly become of interest. Therefore, the ability to quantitatively assess alterations in cholesterol homeostasis resulting from exposure to xenobiotics is of value. This unit describes methods for the quantitative assessment of altered post-squalene cholesterol biosynthesis and subsequent oxysterol formation in various sample types using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Understanding alterations in cholesterol homeostasis resulting from xenobiotic exposure can provide key insight into the toxicant's mechanism of action and resulting phenotype. © 2018 by John Wiley & Sons, Inc.

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