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dc.contributor.authorChaowalit Yuajiten_US
dc.contributor.authorSureeporn Homvisasevongsaen_US
dc.contributor.authorLisa Chatsudthipongen_US
dc.contributor.authorSunhapas Soodvilaien_US
dc.contributor.authorChatchai Muanprasaten_US
dc.contributor.authorVaranuj Chatsudthipongen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherHuachiew Chalermprakiet Universityen_US
dc.date.accessioned2018-10-19T04:31:22Z-
dc.date.available2018-10-19T04:31:22Z-
dc.date.issued2013-03-11en_US
dc.identifier.citationPLoS ONE. Vol.8, No.3 (2013)en_US
dc.identifier.issn19326203en_US
dc.identifier.other2-s2.0-84874867536en_US
dc.identifier.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84874867536&origin=inwarden_US
dc.identifier.urihttp://repository.li.mahidol.ac.th/dspace/handle/123456789/31055-
dc.description.abstractCyst enlargement in polycystic kidney disease (PKD) involves cAMP-activated proliferation of cyst-lining epithelial cells and transepithelial fluid secretion into the cyst lumen via cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. This study aimed to investigate an inhibitory effect and detailed mechanisms of steviol and its derivatives on cyst growth using a cyst model in Madin-Darby canine kidney (MDCK) cells. Among 4 steviol-related compounds tested, steviol was found to be the most potent at inhibiting MDCK cyst growth. Steviol inhibition of cyst growth was dose-dependent; steviol (100 microM) reversibly inhibited cyst formation and cyst growth by 72.5±3.6% and 38.2±8.5%, respectively. Steviol at doses up to 200 microM had no effect on MDCK cell viability, proliferation and apoptosis. However, steviol acutely inhibited forskolin-stimulated apical chloride current in MDCK epithelia, measured with the Ussing chamber technique, in a dose-dependent manner. Prolonged treatment (24 h) with steviol (100 microM) also strongly inhibited forskolin-stimulated apical chloride current, in part by reducing CFTR protein expression in MDCK cells. Interestingly, proteasome inhibitor, MG-132, abolished the effect of steviol on CFTR protein expression. Immunofluorescence studies demonstrated that prolonged treatment (24 h) with steviol (100 microM) markedly reduced CFTR expression at the plasma membrane. Taken together, the data suggest that steviol retards MDCK cyst progression in two ways: first by directly inhibiting CFTR chloride channel activity and second by reducing CFTR expression, in part, by promoting proteasomal degradation of CFTR. Steviol and related compounds therefore represent drug candidates for treatment of polycystic kidney disease. © 2013 Yuajit et al.en_US
dc.rightsMahidol Universityen_US
dc.source.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84874867536&origin=inwarden_US
dc.subjectAgricultural and Biological Sciencesen_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.titleSteviol Reduces MDCK Cyst Formation and Growth by Inhibiting CFTR Channel Activity and Promoting Proteasome-Mediated CFTR Degradationen_US
dc.typeArticleen_US
dc.rights.holderSCOPUSen_US
dc.identifier.doi10.1371/journal.pone.0058871en_US
Appears in Collections:Scopus 2011-2015

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