Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Mitogenic effect of erythropoietin on neonatal rat cardiomyocytes: Signal transduction pathways

Mitogenic effect of erythropoietin on neonatal rat cardiomyocytes: Signal transduction pathways 10.1002/(SICI)1097-4652(199606)167:3<461::AID-JCP10>3.3.CO;2-N The mitogenic effect of recombinant human erythropoietin (rHuEpo) on primary cultures of neonatal rat cardiac myocytes was observed. rHuEpo triggered a dose‐dependent increase in myocyte proliferation. The hormone effect over optimally grown control culture 1 day after addition was maximum with 0.5 U/ml and was inhibited with anti‐rHuEpo. Inhibitors of enzymatic pathways known to be involved in the cytokines intracellular mechanism such as genistein (tyrosine kinase inhibitor), 2‐nitro‐4‐carboxiphenyl‐N,N‐diphenylcarbamate (phospholipase C (PLC) inhibitor), and 1‐(5‐isoquinolinylsufonyl)‐2‐methyl‐piperazine (protein kinase C (PKC) inhibitor) prevented the mitogenic action of rHuEpo. Also the inhibition of Na+‐K+‐ATPase activity by ouabain blunted the stimulatory action of rHuEpo on cell proliferation. The mitogenic action of the hormone was correlated with cardiac membrane paranitrophenilphosphatase (pNPPase) and PKC activity, since concentrations of rHuEpo that stimulate DNA synthesis increased pNPPase and PKC activity. Moreover, the enzymatic inhibition of tyrosine kinase, PLC, and PKC attenuated the stimulatory action of rHuEpo upon cardiac pNPPase activity. In this paper we demonstrate a non‐hematopoietic action of rHuEpo showing both mitogenic and enzymatic effect upon primary myocyte cell culture and on pNPPase activity of neonatal rat heart. These effects are related to the capacity of rHuEpo to stimulate Na+‐K+‐ATPase activity and appear to be secondary to the activation of tyrosine kinase and PKC, indicating that in the rHuEpo mediated mitogenic action on cardiomyocytes involves the activation of the same enzymatic pathways that have been described by other cytokines in different tissues. © 1996 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Cellular Physiology Wiley

Mitogenic effect of erythropoietin on neonatal rat cardiomyocytes: Signal transduction pathways

Download PDF
8 pages

Loading next page...
 
/lp/wiley/mitogenic-effect-of-erythropoietin-on-neonatal-rat-cardiomyocytes-0ElsVP2q2S

References (41)

Publisher
Wiley
Copyright
Copyright © 1996 Wiley‐Liss, Inc.
ISSN
0021-9541
eISSN
1097-4652
DOI
10.1002/(SICI)1097-4652(199606)167:3<461::AID-JCP10>3.0.CO;2-7
Publisher site
See Article on Publisher Site

Abstract

10.1002/(SICI)1097-4652(199606)167:3<461::AID-JCP10>3.3.CO;2-N The mitogenic effect of recombinant human erythropoietin (rHuEpo) on primary cultures of neonatal rat cardiac myocytes was observed. rHuEpo triggered a dose‐dependent increase in myocyte proliferation. The hormone effect over optimally grown control culture 1 day after addition was maximum with 0.5 U/ml and was inhibited with anti‐rHuEpo. Inhibitors of enzymatic pathways known to be involved in the cytokines intracellular mechanism such as genistein (tyrosine kinase inhibitor), 2‐nitro‐4‐carboxiphenyl‐N,N‐diphenylcarbamate (phospholipase C (PLC) inhibitor), and 1‐(5‐isoquinolinylsufonyl)‐2‐methyl‐piperazine (protein kinase C (PKC) inhibitor) prevented the mitogenic action of rHuEpo. Also the inhibition of Na+‐K+‐ATPase activity by ouabain blunted the stimulatory action of rHuEpo on cell proliferation. The mitogenic action of the hormone was correlated with cardiac membrane paranitrophenilphosphatase (pNPPase) and PKC activity, since concentrations of rHuEpo that stimulate DNA synthesis increased pNPPase and PKC activity. Moreover, the enzymatic inhibition of tyrosine kinase, PLC, and PKC attenuated the stimulatory action of rHuEpo upon cardiac pNPPase activity. In this paper we demonstrate a non‐hematopoietic action of rHuEpo showing both mitogenic and enzymatic effect upon primary myocyte cell culture and on pNPPase activity of neonatal rat heart. These effects are related to the capacity of rHuEpo to stimulate Na+‐K+‐ATPase activity and appear to be secondary to the activation of tyrosine kinase and PKC, indicating that in the rHuEpo mediated mitogenic action on cardiomyocytes involves the activation of the same enzymatic pathways that have been described by other cytokines in different tissues. © 1996 Wiley‐Liss, Inc.

Journal

Journal of Cellular Physiology – Wiley

Published: Jun 1, 1996

There are no references for this article.