Linked Life Data

7559390

Source:http://linkedlifedata.com/resource/pubmed/id/7559390

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
1995-11-6
pubmed:abstractText
Tumor necrosis factor alpha (TNF alpha) activates the stress-activated protein kinases (SAPKs, also known as Jun nuclear kinases or JNKs) resulting in the stimulation of AP-1-dependent gene transcription and induces the translocation of NF kappa B to the nucleus resulting in the stimulation of NF kappa B-dependent gene transcription. A potential second messenger for these signaling pathways is ceramide, which is generated when TNF alpha activates sphingomyelinases. We show that treatment of HL-60 human promyelocytic cells with exogenous sphingomyelinase leads to rapid stimulation of JNK/SAPK activity, an effect not mimicked by treatment with phospholipase A2, C, or D. Further, JNK/SAPK activity is stimulated 2.7- and 2.8-fold, respectively, in cells exposed to C2-ceramide (5 microM) or TNF alpha (10 ng/ml). The prolonged stimulation of this kinase activity by C2-ceramide is similar to that previously reported for TNF alpha. In contrast, the related mitogen-activated protein kinases ERK1 and ERK2 are weakly stimulated following TNF alpha treatment (1.5-fold) and are inhibited by C2-ceramide treatment. TNF alpha also potently stimulates NF-kappa B DNA binding activity and transcriptional activity, but these effects are not mimicked by addition of C2-ceramide or sphingomyelinase to intact cells. Furthermore, TNF alpha, sphingomyelinase, and C2-ceramide induce c-jun, a gene that is stimulated by the ATF-2 and c-Jun transcription factors. These data suggest that ceramide may act as a second messenger for a subset of TNF alpha's biochemical and biological effects.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
22689-92
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:7559390-Animals, pubmed-meshheading:7559390-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:7559390-Ceramides, pubmed-meshheading:7559390-Enzyme Activation, pubmed-meshheading:7559390-Gene Expression, pubmed-meshheading:7559390-Genes, jun, pubmed-meshheading:7559390-HL-60 Cells, pubmed-meshheading:7559390-Humans, pubmed-meshheading:7559390-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:7559390-Mice, pubmed-meshheading:7559390-Mitogen-Activated Protein Kinases, pubmed-meshheading:7559390-Proto-Oncogene Proteins c-jun, pubmed-meshheading:7559390-RNA, Messenger, pubmed-meshheading:7559390-Recombinant Proteins, pubmed-meshheading:7559390-Second Messenger Systems, pubmed-meshheading:7559390-Signal Transduction, pubmed-meshheading:7559390-Sphingomyelin Phosphodiesterase, pubmed-meshheading:7559390-Stress, Physiological, pubmed-meshheading:7559390-Tumor Necrosis Factor-alpha
pubmed:year
1995
pubmed:articleTitle
Ceramide activates the stress-activated protein kinases.
pubmed:affiliation
Department of Medicine, University of North Carolina, Chapel Hill 27599-7038, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.