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rdf:type |
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lifeskim:mentions |
umls-concept:C0006675,
umls-concept:C0021547,
umls-concept:C0030685,
umls-concept:C0086597,
umls-concept:C0301625,
umls-concept:C0391871,
umls-concept:C0521447,
umls-concept:C0542341,
umls-concept:C0680255,
umls-concept:C1283071,
umls-concept:C1698986,
umls-concept:C1963578
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pubmed:issue |
23
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pubmed:dateCreated |
2005-6-6
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pubmed:abstractText |
The activation of the transcription factor nuclear factor-kappaB (NF-kappaB) by growth factors, cytokines, and cellular stress can prevent apoptosis, but the underlying mechanism is unknown. Here we provide evidence for an action of NF-kappaB on calcium signaling that accounts for its anti-apoptotic function. Embryonic fibroblasts lacking the transactivating subunit of NF-kappaB RelA (p65) exhibit enhanced inositol 1,4,5-trisphosphate (IP(3)) receptor-mediated calcium release and increased sensitivity to apoptosis, which are restored upon re-expression of RelA. The size of the endoplasmic reticulum (ER) calcium pool and the number of IP(3) receptors per cell are decreased in response to stimuli that activate NF-kappaB and are increased when NF-kappaB activity is suppressed. The selective antagonism of IP(3) receptors blocks apoptosis in RelA-deficient cells, whereas activation of NF-kappaB in normal cells leads to decreased levels of the type 1 IP(3) receptor and decreased calcium release. Overexpression of Bcl-2 normalizes ER calcium homeostasis and prevents calcium-mediated apoptosis in RelA-deficient cells. These findings establish an ER calcium channel as a pivotal target for NF-kappaB-mediated cell survival signaling.
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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/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Transporting ATPases,
http://linkedlifedata.com/resource/pubmed/chemical/Ceramides,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate...,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Sarcoplasmic Reticulum...,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor RelA
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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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 |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
22287-96
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15814613-Adenosine Triphosphate,
pubmed-meshheading:15814613-Animals,
pubmed-meshheading:15814613-Apoptosis,
pubmed-meshheading:15814613-Blotting, Western,
pubmed-meshheading:15814613-Calcium,
pubmed-meshheading:15814613-Calcium Channels,
pubmed-meshheading:15814613-Calcium-Transporting ATPases,
pubmed-meshheading:15814613-Cell Survival,
pubmed-meshheading:15814613-Ceramides,
pubmed-meshheading:15814613-Cytosol,
pubmed-meshheading:15814613-DNA,
pubmed-meshheading:15814613-Endoplasmic Reticulum,
pubmed-meshheading:15814613-Immunoblotting,
pubmed-meshheading:15814613-Immunohistochemistry,
pubmed-meshheading:15814613-Inositol 1,4,5-Trisphosphate,
pubmed-meshheading:15814613-Inositol 1,4,5-Trisphosphate Receptors,
pubmed-meshheading:15814613-Lipid Metabolism,
pubmed-meshheading:15814613-Mice,
pubmed-meshheading:15814613-Mice, Transgenic,
pubmed-meshheading:15814613-Microscopy, Fluorescence,
pubmed-meshheading:15814613-Microsomes,
pubmed-meshheading:15814613-NF-kappa B,
pubmed-meshheading:15814613-Oligonucleotides, Antisense,
pubmed-meshheading:15814613-Oxidative Stress,
pubmed-meshheading:15814613-RNA, Messenger,
pubmed-meshheading:15814613-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:15814613-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15814613-Sarcoplasmic Reticulum Calcium-Transporting ATPases,
pubmed-meshheading:15814613-Signal Transduction,
pubmed-meshheading:15814613-Time Factors,
pubmed-meshheading:15814613-Transcription Factor RelA,
pubmed-meshheading:15814613-Transcriptional Activation
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pubmed:year |
2005
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pubmed:articleTitle |
Suppression of calcium release from inositol 1,4,5-trisphosphate-sensitive stores mediates the anti-apoptotic function of nuclear factor-kappaB.
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pubmed:affiliation |
Laboratory of Neurosciences, National Institute on Aging/NIH, Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. camandolasi@grc.nia.nih.gov
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pubmed:publicationType |
Journal Article
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