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dc.contributor.authorKuntzsch, Dana
dc.contributor.authorBergann, Theresa
dc.contributor.authorDames, Petra
dc.contributor.authorFromm, Anja
dc.contributor.authorFromm, Michael
dc.contributor.authorDavis, Rohan A
dc.contributor.authorMelzig, Matthias F
dc.contributor.authorSchulzke, Joerg D
dc.date.accessioned2017-05-03T12:46:45Z
dc.date.available2017-05-03T12:46:45Z
dc.date.issued2012
dc.date.modified2013-06-25T00:47:35Z
dc.identifier.issn1932-6203
dc.identifier.doi10.1371/journal.pone.0049426
dc.identifier.urihttp://hdl.handle.net/10072/51888
dc.description.abstractIn 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.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent937042 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherPublic Library of Science
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrome49426-1
dc.relation.ispartofpagetoe49426-14
dc.relation.ispartofissue11
dc.relation.ispartofjournalPloS One
dc.relation.ispartofvolume7
dc.rights.retentionY
dc.subject.fieldofresearchBiologically active molecules
dc.subject.fieldofresearchcode340401
dc.titleThe plant-derived glucocorticoid receptor agonist endiandrin A acts as co-stimulator of colonic epithelial sodium channels (ENaC) via SGK-1 and MAPKs
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://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.issued2012
gro.hasfulltextFull Text
gro.griffith.authorDavis, Rohan A.


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