Linked Life Data

9632728

Source:http://linkedlifedata.com/resource/pubmed/id/9632728

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
1998-8-3
pubmed:abstractText
Ceramide is an important lipid messenger involved in mediating a variety of cell functions including apoptosis. However, mechanisms responsible for ceramide-induced apoptosis remain unclear. We investigated the possibility that ceramide may decrease antiapoptotic signaling in cells by inhibiting Akt kinase activity. Our data show that C2-ceramide induces apoptosis in HMN1 motor neuron cells and decreases both basal and insulin- or serum-stimulated Akt kinase activity 65-70%. These results are consistent with decreased Akt kinase activity being involved in the apoptotic effects of ceramide. This possibility is further supported by studies showing that constitutively active Akt kinase decreases C2-ceramide-induced death of HMN1 cells as well as COS-7 cells. Decreased Akt activity is not due to ceramide activating the ceramide-activated protein phosphatase or to a direct inhibition of Akt kinase by ceramide, suggesting that ceramide acts upstream of Akt kinase to decrease its activity. Treating cells with C2-ceramide does not affect phosphorylation of insulin receptor substrate-1, interactions between insulin receptor substrate-1 and p85, or insulin-stimulated phosphatidylinositol 3-kinase activity, suggesting that the effects of C2-ceramide on Akt kinase are not mediated through modulating phosphatidylinositol 3-kinase. In sum, our results suggest that inhibition of the key antiapoptotic kinase, Akt, may play an important role in ceramide-induced apoptosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
16568-75
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Inhibition of Akt kinase by cell-permeable ceramide and its implications for ceramide-induced apoptosis.
pubmed:affiliation
Department of Pharmacology, and Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.