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Oxysterols are derivatives of cholesterol and an important regulator of cholesterol metabolism, in part due to their role as ligands for nuclear receptors, such as the liver x receptors. Oxysterols are also known to be ligands for the RAR-related orphan receptors, involved in normal T cell differentiation. However, increasing evidence supports a role for oxysterols in the progression of several diseases. Here, we review recent developments in oxysterol research, highlighting the biological functions that oxysterols exert through their target nuclear receptors: the liver x receptors, estrogen receptors RAR-related orphan receptor and the glucocorticoid receptor. We also bring the regulation of the immune system into the context of interaction between oxysterols and nuclear receptors, discussing the effect of such interaction on the pro-inflammatory function of macrophages and the development of T cells. Finally, we examine the impact that oxysterols have on various disease models, including cancer, Alzheimer's disease and atherosclerosis, stressing the role of nuclear receptors if previously identified. This review underscores the need to consider the multifaceted roles of oxysterols in terms of multiple receptor engagements and selective modulation of these receptors.
This article was published in the following journal.
Name: Molecular and cellular endocrinology
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Nuclear receptors that bind OXYSTEROLS and function as heterodimers with RETINOID X RECEPTORS. They have important functions in regulating cholesterol homeostasis, ENERGY METABOLISM; INFLAMMATION; and the immune response.
A nuclear co-repressor protein that shows specificity for RETINOIC ACID RECEPTORS and THYROID HORMONE RECEPTORS. The dissociation of this co-repressor from nuclear receptors is generally ligand-dependent, but can also occur by way of its phosphorylation by members of the MAP KINASE SIGNALING SYSTEM. The protein contains two nuclear receptor interaction domains and four repressor domains and is closely-related in structure to NUCLEAR RECEPTOR CO-REPRESSOR 1.
A mediator complex subunit that is believed to play a key role in the coactivation of nuclear receptor-activated transcription by the mediator complex. It interacts with a variety of nuclear receptors including RETINOIC ACID RECEPTORS; THYROID HORMONE RECEPTORS; VITAMIN D RECEPTORS; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; ESTROGEN RECEPTORS; and GLUCOCORTICOID RECEPTORS.
Proteins that enhance gene expression when associated with ligand bound activated NUCLEAR RECEPTORS. The coactivators may act through an enzymatic process that affects the rate of transcription or the structure of chromatin. Alternatively nuclear receptor coactivators can function as adaptor proteins that bring nuclear receptors into close proximity with transcriptional complexes.
A nuclear receptor coactivator with specificity for ESTROGEN RECEPTORS; PROGESTERONE RECEPTORS; and THYROID HORMONE RECEPTORS. It contains a histone acetyltransferase activity that may play a role in the transcriptional activation of chromatin regions.
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...