Hepatocyte-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 beta
DC Field | Value | Language |
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dc.contributor.author | Song, Jae-Sook | - |
dc.contributor.author | Kim, Eun-Kyung | - |
dc.contributor.author | Choi, Yong-Won | - |
dc.contributor.author | Oh, Won Keun | - |
dc.contributor.author | Kim, Young-Mi | - |
dc.date.accessioned | 2021-06-22T16:21:32Z | - |
dc.date.available | 2021-06-22T16:21:32Z | - |
dc.date.created | 2021-01-21 | - |
dc.date.issued | 2016-09 | - |
dc.identifier.issn | 0041-008X | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/13039 | - |
dc.description.abstract | Oxidative 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. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | ACADEMIC PRESS INC ELSEVIER SCIENCE | - |
dc.title | Hepatocyte-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 beta | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Young-Mi | - |
dc.identifier.doi | 10.1016/j.taap.2016.08.003 | - |
dc.identifier.scopusid | 2-s2.0-84981225602 | - |
dc.identifier.wosid | 000382417400015 | - |
dc.identifier.bibliographicCitation | TOXICOLOGY AND APPLIED PHARMACOLOGY, v.307, pp.138 - 149 | - |
dc.relation.isPartOf | TOXICOLOGY AND APPLIED PHARMACOLOGY | - |
dc.citation.title | TOXICOLOGY AND APPLIED PHARMACOLOGY | - |
dc.citation.volume | 307 | - |
dc.citation.startPage | 138 | - |
dc.citation.endPage | 149 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalResearchArea | Toxicology | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Toxicology | - |
dc.subject.keywordPlus | EPITHELIAL-MESENCHYMAL TRANSITION | - |
dc.subject.keywordPlus | MYRISTICA-FRAGRANS NUTMEG | - |
dc.subject.keywordPlus | GLUTATHIONE-S-TRANSFERASE | - |
dc.subject.keywordPlus | TRANSCRIPTION FACTOR NRF2 | - |
dc.subject.keywordPlus | BINDING-PROTEIN-BETA | - |
dc.subject.keywordPlus | INDUCIBLE EXPRESSION | - |
dc.subject.keywordPlus | CELL-PROLIFERATION | - |
dc.subject.keywordPlus | SIGNALING PATHWAY | - |
dc.subject.keywordPlus | LIVER-DISEASE | - |
dc.subject.keywordPlus | SUBUNIT GENE | - |
dc.subject.keywordAuthor | Nectandrin B | - |
dc.subject.keywordAuthor | Hepatocyte protection | - |
dc.subject.keywordAuthor | Nrf2 | - |
dc.subject.keywordAuthor | Antioxidant enzymes | - |
dc.subject.keywordAuthor | GSK-3 beta | - |
dc.subject.keywordAuthor | ERK | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S0041008X16302186?via%3Dihub | - |
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