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Gliotoxin-mediated apoptosis of activated human hepatic stellate cells
DC Field | Value | Language |
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dc.contributor.author | 백용한 | - |
dc.date.accessioned | 2015-07-15T17:06:44Z | - |
dc.date.available | 2015-07-15T17:06:44Z | - |
dc.date.issued | 2003 | - |
dc.identifier.issn | 0168-8278 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/114250 | - |
dc.description.abstract | BACKGROUND: Activated hepatic stellate cells (HSCs) play a central role in liver fibrogenesis, and apoptosis of activated HSCs might be essential to clear HSCs from injured liver. Gliotoxin induces apoptosis of activated human and rat HSCs by an unknown mechanism. AIM: This study investigated the role of reactive oxygen species (ROS) and membrane permeability transition (MPT) in gliotoxin-induced apoptosis of activated human HSCs. METHODS: Primary and immortalized human HSCs were analyzed using confocal microscopy for ROS with dichlorodihdrofluorescence diacetate (DCFH-DA) fluorophore and for the mitochondrial membrane potential (MMP) using tetramethylrhodamine methylester (TMRM). RESULTS: Gliotoxin at higher concentrations (> or =7.5 microM) markedly increased ROS formation, and ROS production was also evident at concentrations of gliotoxin causing necrotic cell death (> or =32.5 microM). Gliotoxin rapidly (begins about 20 min at 1.5 microM and 10 min at 7.5 microM) disrupts MMP at a concentration as low as 300nM. MMP disruption was followed by cytochrome c release and caspase-3 activation. The MPT inhibitors, cyclosporine A (5 microM) plus trifluoperazine (12.5 microM), blocked depolarization of the mitochondrial membrane and release of cytochrome c, but did not block apoptosis in HSCs. CONCLUSIONS: Gliotoxin (0.3-7.5 microM) induces apoptosis of activated human HSCs with induction of MPT, cytochrome c release and caspase-3 activation, whereas at higher doses (>32.5 microM), it induces necrosis. However, gliotoxin also activates a mitochondrial independent pathway. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 38~46 | - |
dc.relation.isPartOf | JOURNAL OF HEPATOLOGY | - |
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 | Adenosine Triphosphate/metabolism | - |
dc.subject.MESH | Annexin A5/metabolism | - |
dc.subject.MESH | Apoptosis/drug effects* | - |
dc.subject.MESH | Caspase 3 | - |
dc.subject.MESH | Caspases/metabolism | - |
dc.subject.MESH | Cell Line, Transformed | - |
dc.subject.MESH | Cyclosporine/pharmacology | - |
dc.subject.MESH | Cytochromes c/metabolism | - |
dc.subject.MESH | Cytosol/metabolism | - |
dc.subject.MESH | Dopamine Antagonists/pharmacology | - |
dc.subject.MESH | Gliotoxin/pharmacology* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Immunosuppressive Agents/pharmacology* | - |
dc.subject.MESH | Liver/cytology* | - |
dc.subject.MESH | Liver Cirrhosis/metabolism | - |
dc.subject.MESH | Liver Cirrhosis/pathology | - |
dc.subject.MESH | Mitochondria/drug effects | - |
dc.subject.MESH | Mitochondria/metabolism | - |
dc.subject.MESH | NF-kappa B/metabolism | - |
dc.subject.MESH | Necrosis | - |
dc.subject.MESH | Oxidative Stress/drug effects | - |
dc.subject.MESH | Protein Binding/drug effects | - |
dc.subject.MESH | Reactive Oxygen Species/metabolism | - |
dc.subject.MESH | Trifluoperazine/pharmacology | - |
dc.title | Gliotoxin-mediated apoptosis of activated human hepatic stellate cells | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학) | - |
dc.contributor.googleauthor | Young-Oh Kweon | - |
dc.contributor.googleauthor | Yong-Han Paik | - |
dc.contributor.googleauthor | David A Brenner | - |
dc.contributor.googleauthor | John J Lemasters | - |
dc.contributor.googleauthor | Ting Qian | - |
dc.contributor.googleauthor | Bernd Schnabl | - |
dc.identifier.doi | 10.1016/S0168-8278(03)00178-8 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A01829 | - |
dc.relation.journalcode | J01441 | - |
dc.identifier.eissn | 1600-0641 | - |
dc.identifier.pmid | 12821042 | - |
dc.identifier.url | http://www.sciencedirect.com/science/article/pii/S0168827803001788 | - |
dc.subject.keyword | Hepatic stellate cells | - |
dc.subject.keyword | Liver fibrosis | - |
dc.subject.keyword | Gliotoxin | - |
dc.subject.keyword | Apoptosis | - |
dc.subject.keyword | Mitochondrial permeability transition | - |
dc.contributor.alternativeName | Paik, Yong Han | - |
dc.contributor.affiliatedAuthor | Paik, Yong Han | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 39 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 38 | - |
dc.citation.endPage | 46 | - |
dc.identifier.bibliographicCitation | JOURNAL OF HEPATOLOGY, Vol.39(1) : 38-46, 2003 | - |
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