PMID: 7528138Dec 1, 1994Paper

Distinct signaling pathways mediate phorbol-ester-induced and cytokine-induced inhibition of erythropoietin gene expression

European Journal of Biochemistry
J FandreyW Jelkmann

Abstract

Hypoxia-induced erythropoietin (Epo) production in vitro is suppressed by interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF) and phorbol esters. Herein, the Epo-synthesizing human hepatoma cell line HepG2 was used to investigate whether protein kinase C (PKC) is involved in the inhibitory action of the cytokines. Within 1 h after the onset of hypoxia, Epo mRNA levels were markedly increased in untreated HepG2 cells as quantitated by competitive reverse transcription PCR. The cytokines IL-1 beta and TNF prevented this hypoxia-induced increase in Epo mRNA levels. In phorbol-ester-treated cells first inhibitory effects on Epo mRNA levels were observed only after 3 h. Western blot analyses revealed the presence of four isoenzymes of PKC in HepG2 cells. None of these isoenzymes was translocated in response to TNF or IL-1 beta, suggesting that the cytokines do not activate PKC in HepG2 cells. In contrast, phorbol esters translocated and, upon prolonged exposure, down-regulated PKC isoenzymes alpha and epsilon. Activation of protein kinase A by dibutyryl-cAMP partially antagonized the cytokine-dependent inhibition of Epo production but did not influence the inhibitory effect of phorbol esters. Endogenous cAMP levels in ...Continue Reading

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Citations

Apr 1, 1996·Pflügers Archiv : European journal of physiology·S FredeW Jelkmann
Sep 3, 1998·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·W Jelkmann
May 25, 2001·Critical Care Medicine·P Hobisch-HagenW Schobersberger
Jan 16, 2004·Critical Care Medicine·Marion Scharte, Mitchell P Fink
Oct 8, 2004·Internal Medicine·Wolfgang Jelkmann
Aug 20, 2011·Pakistan Journal of Biological Sciences : PJBS·P AnandT Balasubramanian
Apr 1, 2010·Journal of Physiology and Biochemistry·A Zembron-LacnyK Szyszka
Jan 15, 1999·Arteriosclerosis, Thrombosis, and Vascular Biology·J ArtsT Kooistra
Sep 12, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Katia La FerlaThomas Hellwig-Bürgel
Nov 1, 1996·European Journal of Haematology·J AbelW Jelkmann
Dec 17, 2020·High Altitude Medicine & Biology·Marissa N BaranauskasRobert F Chapman

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