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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2-3
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pubmed:dateCreated |
1999-1-21
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pubmed:abstractText |
Acetylcholine has been shown to induce proliferation of human astrocytoma cells by activating muscarinic receptors, particularly the m3 subtype. In the present study the role of protein kinase C in DNA synthesis induced by carbachol has been investigated. Carbachol-induced [methyl-3H]thymidine incorporation was inhibited by the protein kinase C inhibitors GF 109203X and staurosporine. However, carbachol-induced DNA synthesis was only partially reduced by protein kinase C down-regulation by phorbol 12-myristate 13-acetate (PMA), and maximal concentrations of carbachol and PMA had an additive effect on [methyl-3H]thymidine incorporation. Exposure for 24 h to maximally effective concentrations of carbachol did not induce down-regulation of protein kinase C alpha, and caused a small but significant down-regulation of protein kinase C epsilon; cells exposed for 24 h to carbachol were still able to respond with protein kinase C translocation to PMA stimulation. Carbachol caused a significant increase of phorbol ester binding, but did not stimulate protein kinase C alpha translocation, while it caused a short-lasting translocation of protein kinase C epsilon; however, protein kinase C epsilon translocation was not correlated with the time-course of carbachol-induced increase in [methyl-3H]thymidine incorporation. On the other hand, the time-course of translocation/down-regulation of protein kinase C alpha and protein kinase C epsilon induced by PMA was in good correlation with the time-course of PMA-induced [methyl-3H]thymidine incorporation. These results suggest that protein kinase C alpha may not be involved in DNA synthesis induced by muscarinic receptors stimulation in 132-1N1 astrocytoma cells, while protein kinase C epsilon appears to play a role in the initial exit from G0/G1 phase, though it cannot be considered the major determinant for sustained proliferation.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Atropine,
http://linkedlifedata.com/resource/pubmed/chemical/Carbachol,
http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Maleimides,
http://linkedlifedata.com/resource/pubmed/chemical/Muscarinic Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Muscarinic Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/PRKCA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PRKCE protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-epsilon,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Muscarinic,
http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/bisindolylmaleimide I
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0014-2999
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
23
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pubmed:volume |
359
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
223-33
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9832394-Astrocytoma,
pubmed-meshheading:9832394-Atropine,
pubmed-meshheading:9832394-Carbachol,
pubmed-meshheading:9832394-Carcinogens,
pubmed-meshheading:9832394-DNA,
pubmed-meshheading:9832394-Dose-Response Relationship, Drug,
pubmed-meshheading:9832394-Down-Regulation,
pubmed-meshheading:9832394-Drug Synergism,
pubmed-meshheading:9832394-Enzyme Inhibitors,
pubmed-meshheading:9832394-Humans,
pubmed-meshheading:9832394-Indoles,
pubmed-meshheading:9832394-Isoenzymes,
pubmed-meshheading:9832394-Maleimides,
pubmed-meshheading:9832394-Muscarinic Agonists,
pubmed-meshheading:9832394-Muscarinic Antagonists,
pubmed-meshheading:9832394-Protein Kinase C,
pubmed-meshheading:9832394-Protein Kinase C-alpha,
pubmed-meshheading:9832394-Protein Kinase C-epsilon,
pubmed-meshheading:9832394-Radioligand Assay,
pubmed-meshheading:9832394-Receptors, Muscarinic,
pubmed-meshheading:9832394-Staurosporine,
pubmed-meshheading:9832394-Tetradecanoylphorbol Acetate,
pubmed-meshheading:9832394-Time Factors,
pubmed-meshheading:9832394-Tumor Cells, Cultured
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pubmed:year |
1998
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pubmed:articleTitle |
The role of protein kinase C alpha and epsilon isozymes in DNA synthesis induced by muscarinic receptors in a glial cell line.
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pubmed:affiliation |
Department of Environmental Health, University of Washington, Seattle 98105, 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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