Linked Life Data

20659502

Source:http://linkedlifedata.com/resource/pubmed/id/20659502

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-9-27
pubmed:abstractText
We previously reported that the anti-tumoral effects of the recombinant IgG(1) antibody 13B8.2, which is directed against the CDR3-like loop on the D1 domain of CD4, are linked to accumulation/retention of CD4 inside membrane rafts, recruitment of signaling molecules of the TCR/CD3 pathway and raft exclusion of the ZAP-70 kinase and its downstream targets Vav-1, PLC?1 and SLP-76. We thus wanted to assess whether this compartmentalization could be related to a possible effect of 13B8.2 on the lipid composition of rafts. Here we show that 13B8.2 treatment of Jurkat T cells did not affect neutral lipids and particularly cholesterol content in GM1-positive membrane rafts, but decreased phosphatidylserine synthesis. C18:0 saturated fatty acid level in GM1-positive membrane rafts and ceramide release were concomitantly increased following treatment with 13B8.2. Antibody-induced ceramide release in membrane rafts occurred through enhanced acid sphingomyelinase activity and was blocked by the acid sphingomyelinase inhibitor imipramine, but was not affected by inhibitors of de novo ceramide synthesis, myriocin and fumonisin B1. Similarly to 13B8.2, addition of bacterial sphingomyelinase increased ceramide release and segregated ZAP-70 outside GM1-positive membrane rafts from Jurkat T cells. Besides CD4/ZAP-70 modulation in membrane rafts, the 13B8.2-induced activation of the acid sphingomyelinase/ceramide pathway is an important event for structuring raft platforms and transducing CD4-related intracellular signals, which can further fine-tune antibody-triggered tumoral effects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1879-0542
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
30
pubmed:volume
133
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
62-9
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
The lipid-modulating effects of a CD4-specific recombinant antibody correlate with ZAP-70 segregation outside membrane rafts.
pubmed:affiliation
IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier F-34298, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't