Linked Life Data

8119915

Source:http://linkedlifedata.com/resource/pubmed/id/8119915

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1994-4-1
pubmed:abstractText
A sphingomyelin (SM)-signaling cycle has been described in human leukemia-derived HL-60 cells (Okazaki, T., Bell, R.M., and Hannun, Y.A. (1989) J. Biol. Chem. 264, 19076-19080). Activation of the cycle by tumor necrosis factor alpha (TNF alpha) occurs rapidly, with peak levels of approximately 30% SM hydrolysis observed within 45-60 min. The mechanisms by which TNF alpha induces this SM turnover remain largely unexplored. In this study, arachidonic acid (AA) was investigated as a potential mediator of TNF alpha effects on SM turnover. In HL-60 cells, 30 nM TNF alpha stimulated the release of AA within 5-10 min. In turn, AA stimulated SM hydrolysis and concomitant ceramide generation within 20 min of addition to cells. Other fatty acids, notably oleate, mimicked the effects of AA on SM hydrolysis, but the methyl ester and alcohol analogs of fatty acids were inactive. Diacylglycerol, a candidate mediator of TNF alpha responses, AA activated a cytosolic sphingomyelinase dose dependently, with 10-100 microM AA including 3-4-fold activation, thus suggesting a direct effect of AA on sphingomyelinase. Melittin, a potent phospholipase A2 activator, induced SM hydrolysis at concentrations as low as 35 nM. However, unlike AA, melittin was unable to stimulate sphingomyelinase activation in an in vitro assay system. Finally, exogenous addition of AA also produced antiproliferative effects reminiscent of ceramide effects. Thus, a role for the phospholipase A2/AA pathway in mediating TNF alpha induction of the SM cycle is supported by multiple lines of evidence. These studies begin to elucidate a mechanism of TNF alpha signaling and identify a close relationship between glycerophospholipid and sphingolipid signaling. AA, therefore, may be pivotal to understanding the sphingomyelin-signaling cascade.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5757-63
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Identification of arachidonic acid as a mediator of sphingomyelin hydrolysis in response to tumor necrosis factor alpha.
pubmed:affiliation
Department of Medicine and Cell Biology, Duke University Medical Center, Durham, North Carolina 27710.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.