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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

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dc.contributor.authorJang, Jung-Hee-
dc.contributor.authorSurh, Young-Joon-
dc.date.accessioned2021-01-31T10:19:59Z-
dc.date.available2021-01-31T10:19:59Z-
dc.date.issued2004-09-
dc.identifier.citationJournal of Biological Chemistry, Vol.279 No.37, pp.38779-38786-
dc.identifier.issn0021-9258-
dc.identifier.other6319-
dc.identifier.urihttps://hdl.handle.net/10371/172834-
dc.description.abstractOxidative 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.titleBcl-2 attenuation of oxidative cell death is associated with up-regulation of gamma-glutamylcysteine ligase via constitutive NF-kappa B activation-
dc.typeArticle-
dc.contributor.AlternativeAuthor서영준-
dc.identifier.doi10.1074/jbc.M406371200-
dc.citation.journaltitleJournal of Biological Chemistry-
dc.identifier.scopusid2-s2.0-4644239177-
dc.citation.endpage38786-
dc.citation.number37-
dc.citation.startpage38779-
dc.citation.volume279-
dc.identifier.urlhttp://www.jbc.org/content/279/37/38779-
dc.identifier.rimsid6319-
dc.identifier.sci000223684100089-
dc.contributor.affiliatedAuthorSurh, Young-Joon-
Appears in Collections:
Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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