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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1996-6-19
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pubmed:abstractText |
Recent study results suggest that protein kinase C [PKC (EC 3.1.4.3)] -dependent up-regulation of c-jun may be involved in leukemic cell programmed cell death, or apoptosis, occurring in response to various chemotherapeutic agents. The current study was undertaken to further evaluate the contribution of c-jun in apoptosis with the use of two highly specific pharmacological inhibitors of PKC (calphostin C and chelerythrine). To address this issue, two human leukemic cell lines, HL-60 and U937, and a U937 subline stably expressing a dominant negative c-jun mutant (TAM67) were exposed to calphostin C and chelerythrine, and c-jun expression was monitored at both the mRNA and protein levels. Both PKC inhibitors induced the classic morphological features of apoptosis as well as internucleosomal DNA degradation in a concentration- and schedule-dependent manner. Concomitant with these changes, unequivocal increases were observed in c-jun mRNA (U937 and HL-60) and protein (U937). In contrast, up-regulation of c-jun mRNA and protein in TAM67-expressing cells exposed to both PKC inhibitors was markedly attenuated relative to effects observed in parental U937 cells. Importantly, despite impaired up-regulation of c-jun at both the message and protein levels, TAM67-expressing cells were equally susceptible to PKC inhibitor-induced apoptosis as parental and empty vector U937 cells. Collectively, these findings raise the possibility that c-jun up-regulation in human myeloid leukemia cells undergoing PKC inhibitor-associated apoptosis represents a response to, rather than a cause of, apoptotic events. They further suggest that this phenomenon involves pathways that do not require PKC activation.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alkaloids,
http://linkedlifedata.com/resource/pubmed/chemical/Benzophenanthridines,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Naphthalenes,
http://linkedlifedata.com/resource/pubmed/chemical/Phenanthridines,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-jun,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/calphostin C,
http://linkedlifedata.com/resource/pubmed/chemical/chelerythrine
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0026-895X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
49
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
788-95
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:8622627-Alkaloids,
pubmed-meshheading:8622627-Apoptosis,
pubmed-meshheading:8622627-Benzophenanthridines,
pubmed-meshheading:8622627-DNA Damage,
pubmed-meshheading:8622627-Enzyme Inhibitors,
pubmed-meshheading:8622627-Gene Expression Regulation,
pubmed-meshheading:8622627-Genes, jun,
pubmed-meshheading:8622627-HL-60 Cells,
pubmed-meshheading:8622627-Humans,
pubmed-meshheading:8622627-Naphthalenes,
pubmed-meshheading:8622627-Phenanthridines,
pubmed-meshheading:8622627-Protein Kinase C,
pubmed-meshheading:8622627-Proto-Oncogene Proteins c-jun,
pubmed-meshheading:8622627-RNA, Messenger,
pubmed-meshheading:8622627-Up-Regulation
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pubmed:year |
1996
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pubmed:articleTitle |
Role of c-jun in human myeloid leukemia cell apoptosis induced by pharmacological inhibitors of protein kinase C.
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pubmed:affiliation |
Department of Medicine, Medical College of Virginia, Richmond 23298, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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