Cited 35 times in
Hirsutenone reduces deterioration of tight junction proteins through EGFR/Akt and ERK1/2 pathway both converging to HO-1 induction
DC Field | Value | Language |
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dc.contributor.author | 천재희 | - |
dc.date.accessioned | 2015-01-06T16:49:29Z | - |
dc.date.available | 2015-01-06T16:49:29Z | - |
dc.date.issued | 2014 | - |
dc.identifier.issn | 0006-2952 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/98840 | - |
dc.description.abstract | Oxidative stress-induced disruption of epithelial tight junctions (TJ) plays a critical role in the pathogenesis of intestinal disorders, including inflammatory bowel disease (IBD). The current study investigated the protective effect of hirsutenone against disruption of the intestinal barrier in vitro and in a mouse model of colitis. Caco-2 cells were stimulated with tert-butyl hydroperoxide (t-BH). Hirsutenone prevented the t-BH-induced increase in permeability by inhibiting the reduction in zonula occludens-1 (ZO-1) expression, and rapidly stimulated tyrosine phosphorylation of the epidermal growth factor receptor (EGFR). Hirsutenone-mediated protection against the loss of ZO-1 depends on the activation of both ERK1/2 and Akt signaling pathways. Interestingly, hirsutenone-mediated activation of Akt, but not ERK1/2, signaling was EGFR-dependent. Hirsutenone increased heme oxygenase-1 (HO-1) expression through both EGFR/Akt- and ERK1/2-dependent pathways, contributing to the protective effects against TJ dysfunction. Colitis was induced in mice by intrarectal administration of 2,4,6,-trinitrobenzene sulfonic acid (TNBS). Hirsutenone administration improved the clinical parameters and tissue histological appearance, increased HO-1 expression, attenuated reduction of ZO-1 and occludin mRNA, and promoted BrdU incorporation in the colonic epithelium of TNBS-treated mice. Taken together, our results demonstrate that hirsutenone reverse disordered intestinal permeability by activating EGFR/Akt and ERK1/2 pathways, which are involved in the regulation of HO-1 expression. These findings highlight the potential of hirsutenone for clinical applications in the treatment of IBD. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 115~125 | - |
dc.relation.isPartOf | BIOCHEMICAL PHARMACOLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Caco-2 Cells | - |
dc.subject.MESH | Catechols/pharmacology* | - |
dc.subject.MESH | Colitis/chemically induced | - |
dc.subject.MESH | Colitis/drug therapy* | - |
dc.subject.MESH | Colitis/genetics | - |
dc.subject.MESH | Colitis/pathology | - |
dc.subject.MESH | Diarylheptanoids/pharmacology* | - |
dc.subject.MESH | Disease Models, Animal | - |
dc.subject.MESH | Gene Expression Regulation | - |
dc.subject.MESH | Heme Oxygenase-1/biosynthesis | - |
dc.subject.MESH | Heme Oxygenase-1/genetics* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Intestinal Mucosa/drug effects | - |
dc.subject.MESH | Intestinal Mucosa/metabolism | - |
dc.subject.MESH | Intestinal Mucosa/pathology | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mitogen-Activated Protein Kinase 3/genetics* | - |
dc.subject.MESH | Mitogen-Activated Protein Kinase 3/metabolism | - |
dc.subject.MESH | Occludin/genetics | - |
dc.subject.MESH | Occludin/metabolism | - |
dc.subject.MESH | Proto-Oncogene Proteins c-akt/genetics* | - |
dc.subject.MESH | Proto-Oncogene Proteins c-akt/metabolism | - |
dc.subject.MESH | RNA, Messenger/genetics* | - |
dc.subject.MESH | RNA, Messenger/metabolism | - |
dc.subject.MESH | Receptor, Epidermal Growth Factor/genetics* | - |
dc.subject.MESH | Receptor, Epidermal Growth Factor/metabolism | - |
dc.subject.MESH | Signal Transduction | - |
dc.subject.MESH | Tight Junction Proteins/metabolism* | - |
dc.subject.MESH | Trinitrobenzenesulfonic Acid | - |
dc.subject.MESH | Zonula Occludens-1 Protein/genetics | - |
dc.subject.MESH | Zonula Occludens-1 Protein/metabolism | - |
dc.subject.MESH | tert-Butylhydroperoxide/pharmacology | - |
dc.title | Hirsutenone reduces deterioration of tight junction proteins through EGFR/Akt and ERK1/2 pathway both converging to HO-1 induction | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학) | - |
dc.contributor.googleauthor | Geom Seog Seo | - |
dc.contributor.googleauthor | Wen-Yi Jiang | - |
dc.contributor.googleauthor | Pil-Hoon Park | - |
dc.contributor.googleauthor | Dong Hwan Sohn | - |
dc.contributor.googleauthor | Jae Hee Cheon | - |
dc.contributor.googleauthor | Sung Hee Lee | - |
dc.identifier.doi | 10.1016/j.bcp.2014.05.006 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A04030 | - |
dc.relation.journalcode | J00283 | - |
dc.identifier.eissn | 1873-2968 | - |
dc.identifier.pmid | 24853984 | - |
dc.identifier.url | http://www.sciencedirect.com/science/article/pii/S0006295214002676 | - |
dc.subject.keyword | Epidermal growth factor receptor | - |
dc.subject.keyword | Heme oxygenase-1 | - |
dc.subject.keyword | Hirsutenone | - |
dc.subject.keyword | Inflammatory bowel diseases | - |
dc.subject.keyword | Tight junction | - |
dc.contributor.alternativeName | Cheon, Jae Hee | - |
dc.contributor.affiliatedAuthor | Cheon, Jae Hee | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 90 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 115 | - |
dc.citation.endPage | 125 | - |
dc.identifier.bibliographicCitation | BIOCHEMICAL PHARMACOLOGY, Vol.90(2) : 115-125, 2014 | - |
dc.identifier.rimsid | 38818 | - |
dc.type.rims | ART | - |
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