Kurtz, Armin, Eckardt, K. U., Pugh, C., Corvol, P., Fabbro, D. and Ratcliffe, P.
(1992)
Phorbol ester inhibits erythropoietin production in human hepatoma cells (Hep G2).
The American journal of physiology. Cell physiology 262 (5 Pt 1), C1204-C1 210.
Date of publication of this fulltext: 04 Dec 2012 13:53at PubMed
Abstract
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) ...
Abstract
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)
Export bibliographical data
| Item type: | Article |
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| Date: | 1992 |
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| Institutions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
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| Identification Number: | | Value | Type |
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| 1317101 | PubMed ID |
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| Classification: | | Notation | Type |
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| 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine | MESH | | Alkaloids/pharmacology | MESH | | Carcinoma, Hepatocellular/ultrastructure | MESH | | Erythropoietin/genetics | MESH | | Humans | MESH | | Isoquinolines/pharmacology | MESH | | Liver Neoplasms/ultrastructure | MESH | | Oxygen/pharmacology | MESH | | Piperazines/pharmacology | MESH | | Protein Kinase C/metabolism | MESH | | RNA, Messenger/metabolism | MESH | | Staurosporine | MESH | | Tetradecanoylphorbol Acetate/pharmacology | MESH | | Tissue Distribution | MESH | | Tumor Cells, Cultured | MESH |
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| Dewey Decimal Classification: | 500 Science > 570 Life sciences
600 Technology > 610 Medical sciences Medicine |
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| Status: | Published |
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| Refereed: | Yes, this version has been refereed |
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| Created at the University of Regensburg: | Unknown |
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| Item ID: | 26948 |
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