rdf:type |
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lifeskim:mentions |
umls-concept:C0007745,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0040715,
umls-concept:C0162638,
umls-concept:C0205263,
umls-concept:C0282549,
umls-concept:C0599718,
umls-concept:C0599813,
umls-concept:C0599893,
umls-concept:C1366876,
umls-concept:C1522702,
umls-concept:C1833235
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pubmed:issue |
1-2
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pubmed:dateCreated |
2008-1-21
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pubmed:abstractText |
Ceramide induces apoptosis through caspase activation, cytochrome c release, and Bax translocation in HL-60 cells. However, the upstream signal transduction pathways that induce Bax translocation during ceramide-mediated apoptosis have not been well defined yet. In this study, the activation of p38 mitogen-activated protein kinase (MAPK) was found to be critical for the induction of apoptosis and subcellular redistribution of Bax. Pharmacological inhibition of p38 MAPK with SB203580 or expression of a dominant-negative p38 MAPK attenuated DNA fragmentation, caspase-3 activation, and Bax translocation in response to ceramide. Overexpression of Akt also led to suppression of Bax translocation to mitochondria during ceramide-induced apoptosis in HL-60 cells. We also provide evidence for cross-talk between p38 MAPK and Akt pathways. Expression of myr-Akt or inhibition of phosphatidylinositol 3-kinase (PI3K) with LY294002 had no effect on p38 MAPK activation by ceramide as assessed by phosphorylation, while inhibition of p38 MAPK by a pharmacological inhibitor or a dominant-negative p38 inhibited Akt dephosphorylation in response to ceramide, suggesting that ceramide-induced p38 MAPK activation negatively regulates the Akt pathway.
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/BAX protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Ceramides,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/SB 203580,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0304-3835
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
260
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
88-95
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18054155-Apoptosis,
pubmed-meshheading:18054155-Caspase 3,
pubmed-meshheading:18054155-Ceramides,
pubmed-meshheading:18054155-Enzyme Activation,
pubmed-meshheading:18054155-HL-60 Cells,
pubmed-meshheading:18054155-Humans,
pubmed-meshheading:18054155-Imidazoles,
pubmed-meshheading:18054155-Leukemia, Promyelocytic, Acute,
pubmed-meshheading:18054155-Mitochondria,
pubmed-meshheading:18054155-Mutation,
pubmed-meshheading:18054155-Phosphorylation,
pubmed-meshheading:18054155-Protein Kinase Inhibitors,
pubmed-meshheading:18054155-Protein Transport,
pubmed-meshheading:18054155-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:18054155-Pyridines,
pubmed-meshheading:18054155-Signal Transduction,
pubmed-meshheading:18054155-Time Factors,
pubmed-meshheading:18054155-Transfection,
pubmed-meshheading:18054155-bcl-2-Associated X Protein,
pubmed-meshheading:18054155-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2008
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pubmed:articleTitle |
Ceramide induces p38 MAPK-dependent apoptosis and Bax translocation via inhibition of Akt in HL-60 cells.
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pubmed:affiliation |
Division of Biochemistry, College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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