|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
3
|
|
pubmed:dateCreated |
1985-10-9
|
|
pubmed:abstractText |
A hybrid toxin composed of ricin A chain and a monoclonal antibody directed against the rat nerve growth factor (NGF) receptor (192-IgG) was prepared using the heterobifunctional cross-linking agent N-succinimidyl-3-(2-pyridyldithio)-propionate and purified by affinity chromatography. Characterization studies showed that the hybrid, 192-s-s-A, displaced bound 125I-labeled 192-IgG from rat superior cervical ganglion (SCG) membranes with an IC50 3-5 times lower than that of unconjugated 192-IgG. When incubated with cultured rat SCG neurons, 192-s-s-A inhibited protein synthesis in a concentration-dependent fashion. The effect of 192-s-s-A on these neurons was reversed by coincubation with an excess of 192-IgG. The IC50 of 192-s-s-A on protein synthesis in rat SCG neurons was 4 nM. Intact ricin and ricin A chain inhibited protein synthesis in these neurons with IC50 values of 5 pM and 500 nM, respectively. The 192-s-s-A hybrid had no effect on mouse SCG neurons or a human melanoma cell line known to have NGF receptors. This is consistent with the finding that 192-IgG recognizes only the rat NGF receptor. Also, 192-s-s-A did not inhibit protein synthesis in primary cultures of rat skeletal muscle or Vero cells, which do not have cell surface receptors for NGF. 192-s-s-A was able to inhibit protein synthesis in PC12 cells but the potency was 10-100 times less in these cells compared to rat SCG neurons. Ricin and A chain were also 10-100 times less potent in PC12 cells than neurons. Rat SCG neurons exposed to 192-s-s-A lost their refractile appearance under phase-contrast optics, showed granular degeneration of neurites, and died. Thus the decreased protein synthesis caused by the hybrid toxin correlated with the morphological destruction of the neurons. 192-s-s-A represents a potentially powerful tool by which to selectively destroy NGF receptor-bearing cells in vitro. The hybrid toxin may prove useful as an in vivo toxin.
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/2993314-2411735,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2993314-3993931,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2993314-4185494,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2993314-4517666,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2993314-5432063,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2993314-6056841,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2993314-6159658,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2993314-6177039,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2993314-6196466,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2993314-6256086,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2993314-6264443,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2993314-6296105,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2993314-6327698,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2993314-6361806,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2993314-6405626,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2993314-6804591,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2993314-6973391,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2993314-7345440,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2993314-762111
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Sep
|
|
pubmed:issn |
0021-9525
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
101
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1107-14
|
|
pubmed:dateRevised |
2009-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:2993314-Animals,
pubmed-meshheading:2993314-Antibodies, Monoclonal,
pubmed-meshheading:2993314-Cells, Cultured,
pubmed-meshheading:2993314-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:2993314-Ganglia, Sympathetic,
pubmed-meshheading:2993314-Nerve Growth Factors,
pubmed-meshheading:2993314-Nerve Tissue Proteins,
pubmed-meshheading:2993314-Neurons,
pubmed-meshheading:2993314-Rats,
pubmed-meshheading:2993314-Receptors, Cell Surface,
pubmed-meshheading:2993314-Receptors, Nerve Growth Factor,
pubmed-meshheading:2993314-Ricin
|
|
pubmed:year |
1985
|
|
pubmed:articleTitle |
Selective destruction of nerve growth factor receptor-bearing cells in vitro using a hybrid toxin composed of ricin A chain and a monoclonal antibody against the nerve growth factor receptor.
|
|
pubmed:publicationType |
Journal Article
|
