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dc.contributor.author김영미-
dc.date.accessioned2018-04-19T01:49:06Z-
dc.date.available2018-04-19T01:49:06Z-
dc.date.issued2016-09-
dc.identifier.citationTOXICOLOGY AND APPLIED PHARMACOLOGY, v. 307, Page. 138-149en_US
dc.identifier.issn0041-008X-
dc.identifier.issn1096-0333-
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S0041008X16302186-
dc.identifier.urihttp://repository.hanyang.ac.kr/handle/20.500.11754/69319-
dc.description.abstractOxidative stress can contribute to the development and progression of liver diseases, such as drug-induced or alcoholic liver injury, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis. Nectandrin B is a bioactive lignan isolated from nutmeg extract. To date, little information is available about its pharmacological activities in the liver. This study investigated the hepatocyte-protective effect of nectandrin B against tert-butylhydroperoxide-induced oxidative injury and the underlying molecular mechanism. The cell viability assay revealed that nectandrin B prevents apoptosis stimulated by tert-butylhydroperoxide in both HepG2 cells and primary mouse hepatocytes. Nectandrin B also attenuated ROS production and restored the depleted glutathione level. Real-time PCR and immunoblot analyses showed that the expression of glutamate-cysteine ligase, an enzyme responsible for the glutathione biosynthesis, was induced by nectandrin B, indicating its indirect antioxidative effect. The NF-E2-related factor-2 (Nrf2) regulates gene expression of an array of antioxidant enzymes in hepatocytes. Nectandrin B stimulated Nrf2 activation as evidenced by its enhanced nuclear accumulation and increased antioxidant response element (ARE)-luciferase activity. Intriguingly, the hepatocyte-protective effect of nectandrin B against oxidative damage was completely abrogated by Nrf2 knockdown using Nrf2 specific siRNA. Nectandrin B promoted ERK activation, but inactivated GSK-3 beta through the AMPK-mediated inhibitory phosphorylation. The enforced overexpression of dominant-negative mutant of MEK1 or AMPK alpha, or wild-type GSK-3 beta inhibited the increase in the NQO1-ARE-luciferase activity stimulated by nectandrin B, suggesting that both ERK and AMPK-GSK-3 beta signalings are involved in the activation of Nrf2/ARE pathway by nectandrin B. Consistent with this, cytoprotection and restoration of glutathione level by nectandrin B was also blocked by the overexpression of dominant-negative MEK1 or wild-type GSK-3 beta. Finally, our data demonstrate that nectandrin B has the ability to protect hepatocytes against oxidative injury through the activation of Nrf2/ARE pathway mediated by ERK phosphorylation and AMPK-dependent inactivation of GSK-3 beta. (C) 2016 Elsevier Inc. All rights reserved.en_US
dc.description.sponsorshipThis work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MSIP)(No. NRF-2014R1A1A1005953).en_US
dc.language.isoen_USen_US
dc.publisherACADEMIC PRESS INC ELSEVIER SCIENCEen_US
dc.subjectNectandrin Ben_US
dc.subjectHepatocyte protectionen_US
dc.subjectNrf2en_US
dc.subjectAntioxidant enzymesen_US
dc.subjectGSK-3 betaen_US
dc.subjectERKen_US
dc.subjectEPITHELIAL-MESENCHYMAL TRANSITIONen_US
dc.subjectMYRISTICA-FRAGRANS NUTMEGen_US
dc.subjectGLUTATHIONE-S-TRANSFERASEen_US
dc.subjectTRANSCRIPTION FACTOR NRF2en_US
dc.subjectBINDING-PROTEIN-BETAen_US
dc.subjectINDUCIBLE EXPRESSIONen_US
dc.subjectCELL-PROLIFERATIONen_US
dc.subjectSIGNALING PATHWAYen_US
dc.subjectLIVER-DISEASEen_US
dc.subjectSUBUNIT GENEen_US
dc.titleHepatocyte-protective effect of nectandrin B, a nutmeg lignan, against oxidative stress: Role of Nrf2 activation through ERK phosphorylation and AMPK-dependent inhibition of GSK-3 betaen_US
dc.typeArticleen_US
dc.relation.volume307-
dc.identifier.doi10.1016/j.taap.2016.08.003-
dc.relation.page138-149-
dc.relation.journalTOXICOLOGY AND APPLIED PHARMACOLOGY-
dc.contributor.googleauthorSong, JS-
dc.contributor.googleauthorKim, EK-
dc.contributor.googleauthorChoi, YW-
dc.contributor.googleauthorOh, WK-
dc.contributor.googleauthorKim, YM-
dc.relation.code2016001754-
dc.sector.campusE-
dc.sector.daehakCOLLEGE OF PHARMACY[E]-
dc.sector.departmentDEPARTMENT OF PHARMACY-
dc.identifier.pidymikim12-
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COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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