Oxysterols: From physiological tuners to pharmacological opportunities
Open Access
- 25 April 2020
- journal article
- review article
- Published by Wiley in British Journal of Pharmacology
- Vol. 178 (16), 3089-3103
- https://doi.org/10.1111/bph.15073
Abstract
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.Funding Information
- National Health and Medical Research Council (APP1139644)
- NSW Health (H19/133660)
- Australian Research Council (DP170101178)
This publication has 114 references indexed in Scilit:
- 11β-Hydroxysteroid dehydrogenase type 1 contributes to the regulation of 7-oxysterol levels in the arterial wall through the inter-conversion of 7-ketocholesterol and 7β-hydroxycholesterolBiochimie, 2013
- The Transcription Factor STAT-1 Couples Macrophage Synthesis of 25-Hydroxycholesterol to the Interferon Antiviral ResponseImmunity, 2013
- Oxysterol sulfation by cytosolic sulfotransferase suppresses liver X receptor/sterol regulatory element binding protein–1c signaling pathway and reduces serum and hepatic lipids in mouse models of nonalcoholic fatty liver diseaseMetabolism, 2012
- Conversion of 7-Dehydrocholesterol to 7-Ketocholesterol Is Catalyzed by Human Cytochrome P450 7A1 and Occurs by Direct Oxidation without an Epoxide IntermediateOnline Journal of Public Health Informatics, 2011
- Oxysterols direct immune cell migration via EBI2Nature, 2011
- Oxysterols direct B-cell migration through EBI2Nature, 2011
- Quantification of Cholesterol-Metabolizing P450s CYP27A1 and CYP46A1 in Neural Tissues Reveals a Lack of Enzyme−Product Correlations in Human Retina but Not Human BrainJournal of Proteome Research, 2010
- 25-Hydroxycholesterol secreted by macrophages in response to Toll-like receptor activation suppresses immunoglobulin A productionProceedings of the National Academy of Sciences of the United States of America, 2009
- High-density lipoprotein protects macrophages from oxidized low-density lipoprotein-induced apoptosis by promoting efflux of 7-ketocholesterol via ABCG1Proceedings of the National Academy of Sciences of the United States of America, 2007
- Enzymatic Reduction of Oxysterols Impairs LXR Signaling in Cultured Cells and the Livers of MiceCell Metabolism, 2007