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rdf:type |
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lifeskim:mentions |
umls-concept:C0007587,
umls-concept:C0007634,
umls-concept:C0023448,
umls-concept:C0109317,
umls-concept:C0752312,
umls-concept:C0752313,
umls-concept:C1150579,
umls-concept:C1333340,
umls-concept:C1366882,
umls-concept:C1370600,
umls-concept:C1517945,
umls-concept:C1704259,
umls-concept:C1705767,
umls-concept:C1705791,
umls-concept:C1705987,
umls-concept:C1720920
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pubmed:issue |
9
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pubmed:dateCreated |
2002-8-15
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pubmed:abstractText |
MEK/ERK-mediated signals have recently been found to inhibit Fas-mediated cell death through inhibition of caspase-8 activity. It remains unknown whether MEK/ERK-mediated signals affect ionizing radiation (IR)-induced cell death. Here we demonstrate that MEK/ERK-mediated signals selectively inhibit IR-induced loss of mitochondrial membrane potential (DeltaPsi(m)) and subsequent cell death. In Jurkat cells, TPA strongly activated ERK and inhibited the IR-induced caspase-8/Bid cleavage and the loss of DeltaPsi(m). The inhibitory effect of TPA was mostly abrogated by pretreatment of a specific MEK inhibitor PD98059, indicating that the effect depends upon MEK/ERK-mediated signals. Moreover, BAF-B03 transfectants expressing IL-2 receptor (IL-2R) beta(c) chain lacking the acidic region, which is responsible for MEK/ERK-mediated signals, revealed higher sensitivity to IR than the transfectants expressing wild-type IL-2R. Interestingly, the signals could neither protect the DeltaPsi(m) loss nor cell death in UV-irradiated cells. These data imply that the anti-apoptotic effect of MEK/ERK-mediated signals appears to selectively inhibit the IR-induced cell death through protection of the DeltaPsi(m) loss. Our data enlighten an anti-apoptotic function of MEK/ERK pathway against IR-induced apoptosis, thereby implying its contribution to radioresistance.
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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/BH3 Interacting Domain Death...,
http://linkedlifedata.com/resource/pubmed/chemical/BID protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/MAP2K1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1350-9047
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
963-71
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12181747-BH3 Interacting Domain Death Agonist Protein,
pubmed-meshheading:12181747-Carrier Proteins,
pubmed-meshheading:12181747-Caspases,
pubmed-meshheading:12181747-Cell Death,
pubmed-meshheading:12181747-Enzyme Inhibitors,
pubmed-meshheading:12181747-Humans,
pubmed-meshheading:12181747-Immunohistochemistry,
pubmed-meshheading:12181747-Interleukin-2,
pubmed-meshheading:12181747-Intracellular Membranes,
pubmed-meshheading:12181747-Jurkat Cells,
pubmed-meshheading:12181747-MAP Kinase Kinase 1,
pubmed-meshheading:12181747-Membrane Potentials,
pubmed-meshheading:12181747-Microscopy, Electron,
pubmed-meshheading:12181747-Mitochondria,
pubmed-meshheading:12181747-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:12181747-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12181747-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12181747-Radiation, Ionizing,
pubmed-meshheading:12181747-Radiation Tolerance,
pubmed-meshheading:12181747-Tetradecanoylphorbol Acetate,
pubmed-meshheading:12181747-Ultraviolet Rays
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pubmed:year |
2002
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pubmed:articleTitle |
MEK/ERK pathway protects ionizing radiation-induced loss of mitochondrial membrane potential and cell death in lymphocytic leukemia cells.
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pubmed:affiliation |
Department of Radiology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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