Griffiths William J, Abdel-Khalik Jonas, Crick Peter J, Yutuc Eylan, Wang Yuqin
College of Medicine, Grove Building, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
College of Medicine, Grove Building, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
J Steroid Biochem Mol Biol. 2016 Sep;162:4-26. doi: 10.1016/j.jsbmb.2015.11.017. Epub 2015 Nov 27.
Oxysterols are oxygenated forms of cholesterol or its precursors. They are formed enzymatically and via reactive oxygen species. Oxysterols are intermediates in bile acid and steroid hormone biosynthetic pathways and are also bioactive molecules in their own right, being ligands to nuclear receptors and also regulators of the processing of steroid regulatory element-binding proteins (SREBPs) to their active forms as transcription factors regulating cholesterol and fatty acid biosynthesis. Oxysterols are implicated in the pathogenesis of multiple disease states ranging from atherosclerosis and cancer to multiple sclerosis and other neurodegenerative diseases including Alzheimer's and Parkinson's disease. Analysis of oxysterols is challenging on account of their low abundance in biological systems in comparison to cholesterol, and due to the propensity of cholesterol to undergo oxidation in air to generate oxysterols with the same structures as those present endogenously. In this article we review the mass spectrometry-based methods for oxysterol analysis paying particular attention to analysis by liquid chromatography-mass spectrometry (LC-MS).
氧化甾醇是胆固醇或其前体的氧化形式。它们通过酶促反应以及活性氧生成。氧化甾醇是胆汁酸和类固醇激素生物合成途径中的中间体，其本身也是生物活性分子，作为核受体的配体，还能调节类固醇调节元件结合蛋白（SREBPs）加工成其作为调节胆固醇和脂肪酸生物合成的转录因子的活性形式。氧化甾醇与多种疾病状态的发病机制有关，范围从动脉粥样硬化、癌症到多发性硬化症以及包括阿尔茨海默病和帕金森病在内的其他神经退行性疾病。由于与胆固醇相比，氧化甾醇在生物系统中的丰度较低，并且由于胆固醇在空气中易于氧化生成与内源性存在的结构相同的氧化甾醇，因此氧化甾醇的分析具有挑战性。在本文中，我们综述了基于质谱的氧化甾醇分析方法，特别关注液相色谱 - 质谱联用（LC - MS）分析。
