Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5 Pt 1
|
pubmed:dateCreated |
1992-6-25
|
pubmed:abstractText |
Using the human hepatoma cell line Hep G2, we have studied a possible role of protein kinase C (PKC) activity for regulation of erythropoietin (EPO) production. During a 72-h incubation, EPO production by the cells was stimulated sevenfold by exposure to low oxygen tension (1%) and threefold by exposure to cobaltous chloride (100 microM). The phorbol ester phorbol 12-myristate-13 acetate (PMA) led to a concentration-dependent inhibition of basal and stimulated EPO formation (ED50 10 nM). This decrease of EPO production, which was apparent already after 1 h of incubation with PMA, reached its maximal effect after 24 h and held on for 72 h. It was paralleled by an inhibition of the increase of EPO mRNA levels in response to stimulation. A 24-h preincubation of the cells with PMA (100 nM) virtually blunted the effect of hypoxia on EPO formation. Recovery of EPO synthesis after removal of PMA took 48-72 h. The effect of PMA on EPO production was mimicked by phorbol 12,13-dibutyrate (ED50 1 microM) but not by 4 alpha-phorbol 12,13-didecanoate. The synthetic diacylglycerol analogues oleolyl-acetylglycerol and dioctanoylglycerol (2-200 microM) also had no effect on either basal or stimulated EPO production. Treatment with PMA caused a translocation of the alpha-isoenzyme of PKC from the cytosol to the membrane after 1 h and a disappearance of the membrane-bound form after 24 h of incubation. Staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, two structurally different inhibitors of PKC activity, inhibited basal and stimulated EPO production with ED50 values of 9 nM and 50 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-(5-Isoquinolinesulfonyl)-2-Methylp...,
http://linkedlifedata.com/resource/pubmed/chemical/Alkaloids,
http://linkedlifedata.com/resource/pubmed/chemical/Erythropoietin,
http://linkedlifedata.com/resource/pubmed/chemical/Isoquinolines,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate
|
pubmed:status |
MEDLINE
|
pubmed:month |
May
|
pubmed:issn |
0002-9513
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
262
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
C1204-10
|
pubmed:dateRevised |
2007-11-15
|
pubmed:meshHeading |
pubmed-meshheading:1317101-1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine,
pubmed-meshheading:1317101-Alkaloids,
pubmed-meshheading:1317101-Carcinoma, Hepatocellular,
pubmed-meshheading:1317101-Erythropoietin,
pubmed-meshheading:1317101-Humans,
pubmed-meshheading:1317101-Isoquinolines,
pubmed-meshheading:1317101-Liver Neoplasms,
pubmed-meshheading:1317101-Oxygen,
pubmed-meshheading:1317101-Piperazines,
pubmed-meshheading:1317101-Protein Kinase C,
pubmed-meshheading:1317101-RNA, Messenger,
pubmed-meshheading:1317101-Staurosporine,
pubmed-meshheading:1317101-Tetradecanoylphorbol Acetate,
pubmed-meshheading:1317101-Tissue Distribution,
pubmed-meshheading:1317101-Tumor Cells, Cultured
|
pubmed:year |
1992
|
pubmed:articleTitle |
Phorbol ester inhibits erythropoietin production in human hepatoma cells (Hep G2).
|
pubmed:affiliation |
Physiologisches Institut, Universität Regensburg, Germany.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|