Linked Life Data

8612652

Source:http://linkedlifedata.com/resource/pubmed/id/8612652

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1996-6-3
pubmed:abstractText
The metabolism and localization of the pools of sphingomyelin and phosphatidylcholine (PtdCho) which are hydrolyzed upon activation of the sphingomyelin signal transduction pathway were studied in human skin fibroblasts treated with tumor necrosis factor alpha (TNF-alpha). In a first series of experiments, cellular phospholipids were labeled with [3H]choline under conditions that inhibit the vesicular traffic to the plasma membrane. Thus, in human fibroblasts metabolically labeled in the presence of brefeldin A, monensin or at 20 degree C, the arrival of newly synthesized sphingomyelin to the cell surface was prevented, supporting previous conclusions for a vesicular mechanism of sphingomyelin transport to the plasma membrane. Under these conditions, TNF-alpha induced the hydrolysis of PtdCho but did not promote the hydrolysis of 3H-labeled sphingomyelin, suggesting that the sphingomyelin signaling pool resides in a compartment distal to the Golgi apparatus, and possibly in the plasma membrane. TNF was also unable to trigger the breakdown of a radioactive sphingomyelin, [ceramide-3H]sphingomyelin, exogenously added to the cells to label the exoplasmic side of the cell surface. However, TNF caused PtdCho and sphingomyelin degradation in fibroblasts that had been treated with bacterial sphingomyelinase to degrade the sphingomyelin pool of the external leaflet of the plasma membrane. A similar result was obtained at 4 degree C, i.e. under conditions which inhibit endocytosis, thereby excluding the endosomes as a potential site for TNF-induced sphingomyelin hydrolysis. Altogether, these results strongly argue for a localization of the sphingomyelin signaling pool at the inner leaflet of the plasma membrane, but neither in the endolyso-somal nor the Golgi compartments. In addition, when [3H]choline-labeled fibroblasts were treated under non-lytic conditions with bacterial phospholipase C to degrade the external pool of PtdCho, TNF was still able to stimulate the hydrolysis of PtdCho. This demonstrates that the pool of PtdCho involved in TNF-alpha signaling (and which is hydrolyzed concurrently with sphingomyelin to generate diacylglycerol), is not located in the outer leaflet of the plasma membrane.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
236
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
738-45
pubmed:dateRevised
2007-7-23
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Comparative study of the metabolic pools of sphingomyelin and phosphatidylcholine sensitive to tumor necrosis factor.
pubmed:affiliation
Laboratoire de Biochimie, "Maladies Métaboliques", Institut Louis Bugnard, Toulouse, France.
pubmed:publicationType
Journal Article, Comparative Study