Wang Yaping, Li Xiaobo, Ren Shunlin
Department of Internal Medicine, McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23249, USA.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Metabolites. 2020 Dec 25;11(1):9. doi: 10.3390/metabo11010009.
Oxysterols have long been believed to be ligands of nuclear receptors such as liver × receptor (LXR), and they play an important role in lipid homeostasis and in the immune system, where they are involved in both transcriptional and posttranscriptional mechanisms. However, they are increasingly associated with a wide variety of other, sometimes surprising, cell functions. Oxysterols have also been implicated in several diseases such as metabolic syndrome. Oxysterols can be sulfated, and the sulfated oxysterols act in different directions: they decrease lipid biosynthesis, suppress inflammatory responses, and promote cell survival. Our recent reports have shown that oxysterol and oxysterol sulfates are paired epigenetic regulators, agonists, and antagonists of DNA methyltransferases, indicating that their function of global regulation is through epigenetic modification. In this review, we explore our latest research of 25-hydroxycholesterol and 25-hydroxycholesterol 3-sulfate in a novel regulatory mechanism and evaluate the current evidence for these roles.
氧化甾醇长期以来被认为是诸如肝脏X受体（LXR）等核受体的配体，它们在脂质稳态和免疫系统中发挥重要作用，在这些系统中，它们参与转录和转录后机制。然而，它们越来越多地与各种各样其他的、有时令人惊讶的细胞功能相关联。氧化甾醇还与多种疾病有关，如代谢综合征。氧化甾醇可以被硫酸化，硫酸化的氧化甾醇作用方向不同：它们可减少脂质生物合成、抑制炎症反应并促进细胞存活。我们最近的报告表明，氧化甾醇和硫酸化氧化甾醇是DNA甲基转移酶的成对表观遗传调节剂、激动剂和拮抗剂，这表明它们的全局调节功能是通过表观遗传修饰实现的。在本综述中，我们探讨了我们对25-羟基胆固醇和25-羟基胆固醇3-硫酸盐在一种新的调节机制方面的最新研究，并评估了这些作用的现有证据。
