Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/38086
DC FieldValueLanguage
dc.contributor.authorHuang, C.C.en_US
dc.contributor.author洪慧芝zh_TW
dc.contributor.authorHsu, P.C.en_US
dc.contributor.authorHung, Y.C.en_US
dc.contributor.authorLiao, Y.F.en_US
dc.contributor.authorLiu, C.C.en_US
dc.contributor.authorHour, C.T.en_US
dc.contributor.authorKao, M.C.en_US
dc.contributor.authorTsay, G.J.en_US
dc.contributor.authorHung, H.C.en_US
dc.contributor.authorLiu, G.Y.en_US
dc.date2005zh_TW
dc.date.accessioned2014-06-06T08:00:29Z-
dc.date.available2014-06-06T08:00:29Z-
dc.identifier.issn1360-8185zh_TW
dc.identifier.urihttp://hdl.handle.net/11455/38086-
dc.description.abstractMethotrexate (MTX), a folate antagonist, was developed for the treatment of malignancies, and is currently used in rheumatoid arthritis (RA) and other chronic inflammatory disorders. It has been proven in short-term and long-term prospective studies that low doses of MTX (0.75 mg/Kg/week) are effective in controlling the inflammatory manifestations of RA. Low-concentrations of MTX achieve apoptosis and clonal deletion of activated peripheral T cells. One of the mechanisms of the anti-inflammatory and immunosuppressive effects may be the production of reactive oxygen species (ROS). However, the drug resistance of MTX in malignancies remains poorly understood. Ornithine decarboxylase (ODC) plays an important role in diverse biological functions, including cell development, differentiation, transformation, growth and apoptosis. In our previous studies, ODC overexpression was shown to prevent TNF alpha-induced apoptosis via reducing ROS. Here, we also investigated one mechanism of MTX-induced apoptosis and of drug resistance as to the anti-apoptotic effects of ODC during MTX treatment. We found MTX could induce caspase-dependent apoptosis and promote ROS generation together with disrupting the mitochondrial membrane potential (Delta Psi(m)) of HL-60 and Jurkat T cells. Putrescine and ROS scavengers could reduce MTX-induced apoptosis, which leads to the loss of Delta Psi(m), through reducing intracellular ROS. Overexpression of ODC in parental cells had the same effects as putrescine and the ROS scavengers. Moreover, ODC overexpression prevented the decline of Bcl-2 that maintains Delta Psi(m), the cytochrome c release and activations of caspase 9 and 3 following MTX treatment. The results demonstrate that MTX-induced apoptosis is ROS-dependent and occurs along a mitochondria-mediated pathway. Overexpressed ODC cells are resistant to MTX-induced apoptosis by reducing intracellular ROS production.en_US
dc.language.isoen_USzh_TW
dc.relationApoptosisen_US
dc.relation.ispartofseriesApoptosis, Volume 10, Issue 4, Page(s) 895-907.en_US
dc.relation.urihttp://dx.doi.org/10.1007/s10495-005-2947-zen_US
dc.subjectapoptosisen_US
dc.subjectcaspaseen_US
dc.subjectmethotrexateen_US
dc.subjectODCen_US
dc.subjectROSen_US
dc.subjectapo-1/fas receptor/ligand systemen_US
dc.subjectdrug-induced apoptosisen_US
dc.subjectcell-deathen_US
dc.subjectchemotherapeutic drugsen_US
dc.subjecthydrogen-peroxideen_US
dc.subjectoxidative stressen_US
dc.subjectt-lymphocytesen_US
dc.subjectnih3t3 cellsen_US
dc.subjectbcl-2en_US
dc.subjectleukemiaen_US
dc.titleOrnithine decarboxylase prevents methotrexate-induced apoptosis by reducing intracellular reactive oxygen species productionen_US
dc.typeJournal Articlezh_TW
dc.identifier.doi10.1007/s10495-005-2947-zzh_TW
item.fulltextno fulltext-
item.languageiso639-1en_US-
item.openairetypeJournal Article-
item.cerifentitytypePublications-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextnone-
Appears in Collections:生命科學系所
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