School of Biotechnology and Biomolecular Sciences, UNSW Sydney, Sydney, New South Wales, Australia.
Garvan Institute of Medical Research and St Vincent's Clinical School, UNSW Sydney, Sydney, New South Wales, Australia.
Br J Pharmacol. 2021 Aug;178(16):3089-3103. doi: 10.1111/bph.15073. Epub 2020 May 17.
Oxysterols are oxygenated forms of cholesterol generated via autooxidation by free radicals and ROS, or formed enzymically by a variety of enzymes such as those involved in the synthesis of bile acids. Although found at very low concentrations in vivo, these metabolites play key roles in health and disease, particularly in development and regulating immune cell responses, by binding to effector proteins such as LXRα, RORγ and Insig and directly or indirectly regulating transcriptional programmes that affect cell metabolism and function. In this review, we summarise the routes by which oxysterols can be generated and subsequently modified to other oxysterol metabolites and highlight their diverse and profound biological functions and opportunities to alter their levels using pharmacological approaches. LINKED ARTICLES: This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc.
氧化固醇是胆固醇通过自由基和 ROS 的自动氧化产生的含氧形式，或者通过各种酶如参与胆汁酸合成的酶酶促形成。尽管在体内浓度非常低，但这些代谢物在健康和疾病中发挥着关键作用，特别是在发育和调节免疫细胞反应中，通过与效应蛋白如 LXRα、RORγ 和 Insig 结合，并直接或间接调节影响细胞代谢和功能的转录程序。在这篇综述中，我们总结了氧化固醇生成的途径，以及随后被修饰为其他氧化固醇代谢物的途径，并强调了它们在生物学功能方面的多样性和深刻性，以及使用药理学方法改变它们水平的机会。相关文章：本文是关于氧化固醇、终身健康和治疗学主题的一部分。要查看本节中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc/。
