Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2008-1-21
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0304-3835
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
260
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
88-95
pubmed:dateRevised
2009-11-19
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
pubmed:year
2008
pubmed:articleTitle
Ceramide induces p38 MAPK-dependent apoptosis and Bax translocation via inhibition of Akt in HL-60 cells.
pubmed:affiliation
Division of Biochemistry, College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't