dc.contributor.author | Kuntzsch, Dana | |
dc.contributor.author | Bergann, Theresa | |
dc.contributor.author | Dames, Petra | |
dc.contributor.author | Fromm, Anja | |
dc.contributor.author | Fromm, Michael | |
dc.contributor.author | Davis, Rohan A | |
dc.contributor.author | Melzig, Matthias F | |
dc.contributor.author | Schulzke, Joerg D | |
dc.date.accessioned | 2017-05-03T12:46:45Z | |
dc.date.available | 2017-05-03T12:46:45Z | |
dc.date.issued | 2012 | |
dc.date.modified | 2013-06-25T00:47:35Z | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.doi | 10.1371/journal.pone.0049426 | |
dc.identifier.uri | http://hdl.handle.net/10072/51888 | |
dc.description.abstract | In a search for secondary plant compounds that bind to the glucocorticoid receptor (GR), the cyclobutane lignan endiandrin A was discovered from the rainforest tree Endiandra anthropophagorum Domin. Our present study aims to characterize the effect of endiandrin A on GR-dependent induction of colonic sodium transport. The effect of endiandrin A was analyzed in GR-expressing colonic HT-29/B6 cells (HT-29/B6-GR). GR transactivation and subcellular localization were investigated by reporter gene assay and immunofluorescence. Epithelial sodium channel (ENaC) was analyzed by qRT-PCR and by measuring amiloride-sensitive short-circuit current (Isc) in Ussing chambers. Endiandrin A (End A) has been identified as GR receptor binder. However, it did not cause significant GR transactivation as pGRE-luciferase activity was only 7% of that of the maximum effect of dexamethasone. Interestingly, endiandrin A had a significant impact on dexamethasone-dependent sodium absorption in cells co-exposed to tumor necrosis factor (TNF)-a. This was in part due to up-regulation of ߭ and ?-ENaC subunit expression. Endiandrin A potentiated GR-mediated transcription by increasing GR protein expression and phosphorylation. It inhibited c-Jun N-terminal kinase (JNK) activation induced by dexamethasone and/or TNF-a and increased levels of GR localized to the nucleus. Additionally, endiandrin A increased the serum- and glucocorticoid-induced kinase (sgk)-1 via activation of p38. Finally, the regulation of ENaC function by endiandrin A was confirmed in rat native colon. In conclusion, endiandrin A potentiates glucocorticoid-driven activation of colonic epithelial sodium channels via JNK inhibition and p38 activation due to transcriptional up-regulation of ߭ and ?-ENaC-subunits along with induction of sgk-1. | |
dc.description.peerreviewed | Yes | |
dc.description.publicationstatus | Yes | |
dc.format.extent | 937042 bytes | |
dc.format.mimetype | application/pdf | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Public Library of Science | |
dc.publisher.place | United States | |
dc.relation.ispartofstudentpublication | N | |
dc.relation.ispartofpagefrom | e49426-1 | |
dc.relation.ispartofpageto | e49426-14 | |
dc.relation.ispartofissue | 11 | |
dc.relation.ispartofjournal | PloS One | |
dc.relation.ispartofvolume | 7 | |
dc.rights.retention | Y | |
dc.subject.fieldofresearch | Biologically active molecules | |
dc.subject.fieldofresearchcode | 340401 | |
dc.title | The plant-derived glucocorticoid receptor agonist endiandrin A acts as co-stimulator of colonic epithelial sodium channels (ENaC) via SGK-1 and MAPKs | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
dcterms.license | http://www.plos.org/journals/license.html | |
gro.rights.copyright | © 2012 Kuntzsch et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License CCAL. (http://www.plos.org/journals/license.html) | |
gro.date.issued | 2012 | |
gro.hasfulltext | Full Text | |
gro.griffith.author | Davis, Rohan A. | |