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Bcl-2 attenuation of oxidative cell death is associated with up-regulation of gamma-glutamylcysteine ligase via constitutive NF-kappa B activation
DC Field | Value | Language |
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dc.contributor.author | Jang, Jung-Hee | - |
dc.contributor.author | Surh, Young Joon | - |
dc.date.accessioned | 2021-01-31T10:19:59Z | - |
dc.date.available | 2021-01-31T10:19:59Z | - |
dc.date.created | 2017-11-16 | - |
dc.date.issued | 2004-09 | - |
dc.identifier.citation | Journal of Biological Chemistry, Vol.279 No.37, pp.38779-38786 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.other | 6319 | - |
dc.identifier.uri | https://hdl.handle.net/10371/172834 | - |
dc.description.abstract | Oxidative stress induced by reactive oxygen intermediates often causes cell death via apoptosis, which is regulated by many functional genes and their protein products. The evolutionarily conserved protein Bcl-2 blocks apoptosis induced by a wide array of death signals. Despite extensive research, the molecular milieu that characterizes the anti-apoptotic function of Bcl-2 has not been fully clarified. In this work, we have investigated the role of bcl-2 in protecting against oxidative death induced by H2O2 in cultured rat pheochromocytoma PC12 cells. Transfection with the bcl-2 gene rescued PC12 cells from apoptotic death caused by H2O2. Addition of NF-kappaB inhibitors such as pyrrolidine dithiocarbamate and N-tosyl-L-phenylalanine chloromethyl ketone to the medium aggravated oxidative cell death. PC12 cells overexpressing bcl-2 exhibited relatively high constitutive DNA binding and transcriptional activities of NF-kappaB compared with vector-transfected control cells. Western blot analysis and immunocytochemistry revealed that bcl-2-transfected PC12 cells retained a higher level of p65 (the functionally active subunit of NF-kappaB) in the nucleus compared with vector-transfected controls. In addition, sustained activation of ERK1/2 (upstream of NF-kappaB) was observed in bcl-2-overexpressing cells. In contrast, the cytoplasmic inhibitor IkappaBalpha was present in lower amounts in cells overexpressing bcl-2. The ectopic expression of bcl-2 increased the cellular glutathione level and gamma-glutamylcysteine ligase expression, which were attenuated by NF-kappaB inhibitors. These results suggest that NF-kappaB plays a role in bcl-2-mediated protection against H2O2-induced apoptosis in PC12 cells through augmentation of antioxidant capacity. | - |
dc.language | 영어 | - |
dc.publisher | American Society for Biochemistry and Molecular Biology Inc. | - |
dc.title | Bcl-2 attenuation of oxidative cell death is associated with up-regulation of gamma-glutamylcysteine ligase via constitutive NF-kappa B activation | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 서영준 | - |
dc.identifier.doi | 10.1074/jbc.M406371200 | - |
dc.citation.journaltitle | Journal of Biological Chemistry | - |
dc.identifier.wosid | 000223684100089 | - |
dc.identifier.scopusid | 2-s2.0-4644239177 | - |
dc.citation.endpage | 38786 | - |
dc.citation.number | 37 | - |
dc.citation.startpage | 38779 | - |
dc.citation.volume | 279 | - |
dc.identifier.sci | 000223684100089 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Surh, Young Joon | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | HYDROGEN-PEROXIDE | - |
dc.subject.keywordPlus | INDUCED APOPTOSIS | - |
dc.subject.keywordPlus | 5&apos | - |
dc.subject.keywordPlus | -FLANKING REGION | - |
dc.subject.keywordPlus | MULTIPLE-MYELOMA | - |
dc.subject.keywordPlus | FREE-RADICALS | - |
dc.subject.keywordPlus | MAP KINASES | - |
dc.subject.keywordPlus | PC-12 CELLS | - |
dc.subject.keywordPlus | PC12 CELLS | - |
dc.subject.keywordPlus | SURVIVAL | - |
dc.subject.keywordPlus | STRESS | - |
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