Herron Josi, Hines Kelly M, Xu Libin
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington.
Department of Medicinal Chemistry, University of Washington, Seattle, Washington.
Curr Protoc Toxicol. 2018 Nov;78(1):e65. doi: 10.1002/cptx.65. Epub 2018 Oct 15.
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.
胆固醇及胆固醇衍生的氧化甾醇对胚胎发育、突触形成与功能以及髓鞘形成等多种生物学功能至关重要。实际上，胆固醇、甾醇前体及氧化甾醇水平的改变会导致多种发育障碍，这凸显了胆固醇稳态的重要性。外源性物质通过改变胆固醇稳态来重现相似表型的能力越来越受到关注。因此，定量评估接触外源性物质导致的胆固醇稳态改变的能力具有重要价值。本单元介绍了使用超高效液相色谱 - 串联质谱法（UHPLC-MS/MS）对各种样品类型中鲨烯后胆固醇生物合成改变及随后氧化甾醇形成进行定量评估的方法。了解外源性物质暴露导致的胆固醇稳态改变可为深入了解毒物的作用机制及由此产生的表型提供关键线索。© 2018 约翰威立国际出版公司
