Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1994-12-27
pubmed:abstractText
The cytotoxic effects of TNF on malignant cells are known to be mediated through high affinity surface receptors. The precise mechanism by which transformed cells are selectively killed by the activation of these receptors is yet unknown, but several intracellular signaling pathways are known to be involved. Phospholipase A2 activation by TNF-alpha has been shown to be important in the transduction of signals leading to cell death. We have used monitoring of extracellular acidification rate as a measure of cellular metabolism to follow the early time course of TNF effects on a human leukemic T cell line (CEM-SS cells). CEM-SS cells were relatively resistant to TNF cell killing but TNF caused an early stimulation of metabolism within 2-4 hr, followed by a suppression of metabolic activity occurring over 20 hr. In contrast, a TNF sensitive subclone of CEM cells (C1Ca) showed a rapid and dramatic decrease in metabolic activity corresponding to cytotoxicity within 18 hr. It was discovered that cupric o-phenanthroline markedly potentiated the effects of TNF on the resistant CEM-SS cells leading to cell death. This observation was specific for copper because ferric o-phenanthroline was without effect at the same concentration. The copper cytotoxic effect was shown to be mediated through the TNF-R1 receptor and independent of phospholipase A2 signaling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9541
pubmed:author
pubmed:issnType
Print
pubmed:volume
161
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
597-605
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:7962141-Animals, pubmed-meshheading:7962141-Cell Line, pubmed-meshheading:7962141-Cell Survival, pubmed-meshheading:7962141-Copper, pubmed-meshheading:7962141-Drug Synergism, pubmed-meshheading:7962141-Flow Cytometry, pubmed-meshheading:7962141-Hydrogen-Ion Concentration, pubmed-meshheading:7962141-Leukemia, T-Cell, pubmed-meshheading:7962141-Metals, pubmed-meshheading:7962141-Oxidation-Reduction, pubmed-meshheading:7962141-Phenanthrolines, pubmed-meshheading:7962141-Quinacrine, pubmed-meshheading:7962141-Rats, pubmed-meshheading:7962141-Reactive Oxygen Species, pubmed-meshheading:7962141-Receptor Aggregation, pubmed-meshheading:7962141-Receptors, Tumor Necrosis Factor, pubmed-meshheading:7962141-Signal Transduction, pubmed-meshheading:7962141-Tumor Cells, Cultured, pubmed-meshheading:7962141-Tumor Necrosis Factor-alpha
pubmed:year
1994
pubmed:articleTitle
Activation of TNF-R1 receptor in the presence of copper kills TNF resistant CEM leukemic T cells.
pubmed:affiliation
Molecular Devices Corporation, Sunnyvale, California 94089.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.