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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
37
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pubmed:dateCreated |
2004-9-6
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pubmed:abstractText |
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 H(2)O(2) in cultured rat pheochromocytoma PC12 cells. Transfection with the bcl-2 gene rescued PC12 cells from apoptotic death caused by H(2)O(2). 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 H(2)O(2)-induced apoptosis in PC12 cells through augmentation of antioxidant capacity.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamate-Cysteine Ligase,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
38779-86
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15208316-Animals,
pubmed-meshheading:15208316-Antioxidants,
pubmed-meshheading:15208316-Apoptosis,
pubmed-meshheading:15208316-Blotting, Western,
pubmed-meshheading:15208316-Cell Death,
pubmed-meshheading:15208316-Cell Line, Tumor,
pubmed-meshheading:15208316-Cell Nucleus,
pubmed-meshheading:15208316-Cell Survival,
pubmed-meshheading:15208316-Cytoplasm,
pubmed-meshheading:15208316-DNA,
pubmed-meshheading:15208316-Dose-Response Relationship, Drug,
pubmed-meshheading:15208316-Enzyme Activation,
pubmed-meshheading:15208316-Glutamate-Cysteine Ligase,
pubmed-meshheading:15208316-Glutathione,
pubmed-meshheading:15208316-Hydrogen Peroxide,
pubmed-meshheading:15208316-I-kappa B Proteins,
pubmed-meshheading:15208316-Immunohistochemistry,
pubmed-meshheading:15208316-In Situ Nick-End Labeling,
pubmed-meshheading:15208316-Luciferases,
pubmed-meshheading:15208316-Membrane Potentials,
pubmed-meshheading:15208316-Mitochondria,
pubmed-meshheading:15208316-Mitogen-Activated Protein Kinases,
pubmed-meshheading:15208316-NF-kappa B,
pubmed-meshheading:15208316-Oxidative Stress,
pubmed-meshheading:15208316-Oxygen,
pubmed-meshheading:15208316-PC12 Cells,
pubmed-meshheading:15208316-Protein Binding,
pubmed-meshheading:15208316-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:15208316-Rats,
pubmed-meshheading:15208316-Transfection,
pubmed-meshheading:15208316-Up-Regulation
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pubmed:year |
2004
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pubmed:articleTitle |
Bcl-2 attenuation of oxidative cell death is associated with up-regulation of gamma-glutamylcysteine ligase via constitutive NF-kappaB activation.
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pubmed:affiliation |
Laboratory of Biochemistry and Molecular Toxicology, College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, Seoul 151-742, South Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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