Activation of AMP-Activated Protein Kinase by a Plant-Derived Dihydroisosteviol in Human Intestinal Epithelial Cell
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概要
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Our previous study has shown that dihydroisosteviol (DHIS), a derivative of stevioside isolated from Stevia rebaudiana (Bertoni), inhibits cystic fibrosis transmembrane conductance regulator (CFTR)-mediated transepithelial chloride secretion across monolayers of human intestinal epithelial (T84) cells and prevents cholera toxin-induced intestinal fluid secretion in mouse closed loop models. In this study, we aimed to investigate a mechanism by which DHIS inhibits CFTR activity. Apical chloride current measurements in Fisher rat thyroid cells stably transfected with wild-type human CFTR (FRT-CFTR cells) and T84 cells were used to investigate mechanism of CFTR inhibition by DHIS. In addition, effect of DHIS on AMP-activated protein kinase (AMPK) activation was investigated using Western blot analysis. Surprisingly, it was found that DHIS failed to inhibit CFTR-mediated apical chloride current in FRT-CFTR cells. In contrast, DHIS effectively inhibited CFTR-mediated apical chloride current induced by a cell permeable cAMP analog CPT-cAMP and a direct CFTR activator genistein in T84 cell monolayers. Interestingly, this inhibitory effect of DHIS on CFTR was significantly (p<0.05) reduced by pretreatment with compound C, an AMPK inhibitor. AICAR, a known AMPK activator, was able to inhibit CFTR activity in both FRT-CFTR and T84 cells. Western blot analysis showed that DHIS induced AMPK activation in T84 cells, but not in FRT-CFTR cells. Our results indicate that DHIS inhibits CFTR-mediated chloride secretion in T84 cells, in part, by activation of AMPK activity. DHIS therefore represents a novel candidate of AMPK activators.
著者
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Suksamrarn Apichart
Department Of Chemistry And Center Of Excellence For Innovation In Chemistry Faculty Of Science Ramk
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Muanprasat Chatchai
Department Of Physiology Faculty Of Science Mahidol University
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Chatsudthipong Varanuj
Department Of Physiology Mahidol University
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Chatsudthipong Varanuj
Department of Physiology, Faculty of Science, Mahidol University
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Muanprasat Chatchai
Department of Physiology, Faculty of Science, Mahidol University
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Sirianant Lalida
Research Center of Transport Protein for Medical Innovation, Faculty of Science, Mahidol University
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Sawasvirojwong Sutthipong
Department of Physiology, Faculty of Science, Mahidol University
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Homvisasevongsa Sureeporn
Division of Physical Science, Faculty of Science and Technology, Huachiew Chalermprakiet University
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- Activation of AMP-Activated Protein Kinase by a Plant-Derived Dihydroisosteviol in Human Intestinal Epithelial Cell