Cargando…
Ouabagenin is a naturally occurring LXR ligand without causing hepatic steatosis as a side effect
Ouabagenin (OBG) is an aglycone of the cardiotonic steroid ouabain and until now was considered a biologically inactive biosynthetic precursor. Herein, we revealed that OBG functions as a novel class of ligand for the liver X receptor (LXR). Luciferase reporter assays and in silico docking studies s...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797171/ https://www.ncbi.nlm.nih.gov/pubmed/29396543 http://dx.doi.org/10.1038/s41598-018-20663-z |
_version_ | 1783297627353251840 |
---|---|
author | Tamura, Satoru Okada, Maiko Kato, Shigeaki Shinoda, Yasuharu Shioda, Norifumi Fukunaga, Kohji Ui-Tei, Kumiko Ueda, Minoru |
author_facet | Tamura, Satoru Okada, Maiko Kato, Shigeaki Shinoda, Yasuharu Shioda, Norifumi Fukunaga, Kohji Ui-Tei, Kumiko Ueda, Minoru |
author_sort | Tamura, Satoru |
collection | PubMed |
description | Ouabagenin (OBG) is an aglycone of the cardiotonic steroid ouabain and until now was considered a biologically inactive biosynthetic precursor. Herein, we revealed that OBG functions as a novel class of ligand for the liver X receptor (LXR). Luciferase reporter assays and in silico docking studies suggested that OBG has LXR-selective agonistic activity. In addition, OBG repressed the expression of epithelial sodium channel (ENaC), a LXR target gene, without causing hepatic steatosis, a typical side effect of conventional LXR ligands. This remarkable biological activity can be attributed to a unique mode of action; the LXR agonist activity mainly proceeds through the LXRβ subtype without affecting LXRα, unlike conventional LXR ligands. Thus, OBG is a novel class of LXR ligand that does not cause severe side effects, with potential for use as an antihypertensive diuretic or a tool compound for exploring LXR subtype-specific biological functions. |
format | Online Article Text |
id | pubmed-5797171 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57971712018-02-13 Ouabagenin is a naturally occurring LXR ligand without causing hepatic steatosis as a side effect Tamura, Satoru Okada, Maiko Kato, Shigeaki Shinoda, Yasuharu Shioda, Norifumi Fukunaga, Kohji Ui-Tei, Kumiko Ueda, Minoru Sci Rep Article Ouabagenin (OBG) is an aglycone of the cardiotonic steroid ouabain and until now was considered a biologically inactive biosynthetic precursor. Herein, we revealed that OBG functions as a novel class of ligand for the liver X receptor (LXR). Luciferase reporter assays and in silico docking studies suggested that OBG has LXR-selective agonistic activity. In addition, OBG repressed the expression of epithelial sodium channel (ENaC), a LXR target gene, without causing hepatic steatosis, a typical side effect of conventional LXR ligands. This remarkable biological activity can be attributed to a unique mode of action; the LXR agonist activity mainly proceeds through the LXRβ subtype without affecting LXRα, unlike conventional LXR ligands. Thus, OBG is a novel class of LXR ligand that does not cause severe side effects, with potential for use as an antihypertensive diuretic or a tool compound for exploring LXR subtype-specific biological functions. Nature Publishing Group UK 2018-02-02 /pmc/articles/PMC5797171/ /pubmed/29396543 http://dx.doi.org/10.1038/s41598-018-20663-z Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Tamura, Satoru Okada, Maiko Kato, Shigeaki Shinoda, Yasuharu Shioda, Norifumi Fukunaga, Kohji Ui-Tei, Kumiko Ueda, Minoru Ouabagenin is a naturally occurring LXR ligand without causing hepatic steatosis as a side effect |
title | Ouabagenin is a naturally occurring LXR ligand without causing hepatic steatosis as a side effect |
title_full | Ouabagenin is a naturally occurring LXR ligand without causing hepatic steatosis as a side effect |
title_fullStr | Ouabagenin is a naturally occurring LXR ligand without causing hepatic steatosis as a side effect |
title_full_unstemmed | Ouabagenin is a naturally occurring LXR ligand without causing hepatic steatosis as a side effect |
title_short | Ouabagenin is a naturally occurring LXR ligand without causing hepatic steatosis as a side effect |
title_sort | ouabagenin is a naturally occurring lxr ligand without causing hepatic steatosis as a side effect |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797171/ https://www.ncbi.nlm.nih.gov/pubmed/29396543 http://dx.doi.org/10.1038/s41598-018-20663-z |
work_keys_str_mv | AT tamurasatoru ouabageninisanaturallyoccurringlxrligandwithoutcausinghepaticsteatosisasasideeffect AT okadamaiko ouabageninisanaturallyoccurringlxrligandwithoutcausinghepaticsteatosisasasideeffect AT katoshigeaki ouabageninisanaturallyoccurringlxrligandwithoutcausinghepaticsteatosisasasideeffect AT shinodayasuharu ouabageninisanaturallyoccurringlxrligandwithoutcausinghepaticsteatosisasasideeffect AT shiodanorifumi ouabageninisanaturallyoccurringlxrligandwithoutcausinghepaticsteatosisasasideeffect AT fukunagakohji ouabageninisanaturallyoccurringlxrligandwithoutcausinghepaticsteatosisasasideeffect AT uiteikumiko ouabageninisanaturallyoccurringlxrligandwithoutcausinghepaticsteatosisasasideeffect AT uedaminoru ouabageninisanaturallyoccurringlxrligandwithoutcausinghepaticsteatosisasasideeffect |