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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1998-12-3
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pubmed:abstractText |
We have previously shown that apoptosis induced in thymocytes by dexamethasone or teniposide (VM-26) could be inhibited by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) and sangivamycin, both relatively specific inhibitors for protein kinase C, but not by N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004), a more specific inhibitor for cAMP-dependent protein kinases. Apoptosis in this model system was not blocked by EGTA and no increase in cytosolic Ca2+ was observed during apoptosis induced by either dexamethasone or VM-26, suggesting that this kinase was Ca2+-independent. In the present study, we demonstrate that addition of 10 microM sangivamycin to thymocyte cultures up to 2 h after addition of either inducer resulted in virtually complete inhibition of apoptosis. Addition of 10 microM sangivamycin at 3 or 4 h after addition of inducer resulted in partial inhibition of apoptosis. Computerized image analysis of two-dimensional PAGE analyses of whole-cell lysates demonstrated that treatment of mouse thymocytes with VM-26 resulted in a limited number of de novo phosphorylation events within 1 h of treatment. The most prominent phosphorylation events associated with VM-26-induced apoptosis were that two intracellular protein species (Protein 1: m.w. = 22.9 kDa, pI, 5.11; and Protein 2: m.w. = 22.9 kDa, pI, 4.98). Similar phosphorylation events were seen in cells treated with dexamethasone. Finally, Western blot analysis suggests that de novo protein phosphorylation induced by VM-26 is on serine/threonine residues. These results provide further evidence that the mechanism of VM-26-induced apoptosis of murine thymocytes involves the action of one or more serine/threonine kinases.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Podophyllotoxin,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Teniposide
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0090-1229
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 1998 Academic Press.
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pubmed:issnType |
Print
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pubmed:volume |
89
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
117-25
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:9787113-Animals,
pubmed-meshheading:9787113-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:9787113-Apoptosis,
pubmed-meshheading:9787113-Dexamethasone,
pubmed-meshheading:9787113-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:9787113-Enzyme Activation,
pubmed-meshheading:9787113-Enzyme Inhibitors,
pubmed-meshheading:9787113-Female,
pubmed-meshheading:9787113-Mice,
pubmed-meshheading:9787113-Mice, Inbred C3H,
pubmed-meshheading:9787113-Phosphorylation,
pubmed-meshheading:9787113-Podophyllotoxin,
pubmed-meshheading:9787113-Protein Kinase C,
pubmed-meshheading:9787113-Protein-Serine-Threonine Kinases,
pubmed-meshheading:9787113-Teniposide,
pubmed-meshheading:9787113-Thymus Gland
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pubmed:year |
1998
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pubmed:articleTitle |
Protein phosphorylation associated with epipodophyllotoxin-induced apoptosis of lymphoid cells: role of a serine/threonine protein kinase.
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pubmed:affiliation |
Department of Microbiology and Immunology, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania, 19131, USA.
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pubmed:publicationType |
Journal Article
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