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Erythropoietin protects the infant heart against ischemia-reperfusion injury by triggering multiple signaling pathways. Basic Res Cardiol 2005 May;100(3):187-97

Date

12/22/2004

Pubmed ID

15611843

DOI

10.1007/s00395-004-0508-1

Scopus ID

2-s2.0-25144473718   93 Citations

Abstract

The immediate protective effect of erythropoietin (EPO) against ischemia in heart suggests a role beyond hematopoiesis and the treatment of anemia. We determined the role of JAK/STAT and Ras/Rac/MAPK in the protective effect of EPO against ischemia-reperfusion injury in infant rabbit heart. EPO (1.0 U/ml) administered 15 minutes prior to 30-minutes global ischemia and 35 minutes reperfusion resulted in increased recovery of postischemic ventricular developed pressure in rabbit hearts. EPO exerted its immediate cardioprotective effect via activation of multiple signaling pathways by: 1) phosphorylation and activation of JAK1/2, STAT3 and STAT5A but not of STAT1alpha and STAT5B, 2) phosphorylation and activation of PI(3) kinase and its downstream kinases Akt and Rac, 3) activation of PKCepsilon, Raf, MEK1/2, p42/44 MAPK and p38 MAPK. Pretreatment with Wortmannin abolished EPO-induced Akt activation and phosphorylation. Pretreatment with Chelerythrine followed by EPO treatment resulted in partial inhibition of Raf activation, and abolished PKCepsilon and p38 MAPK activation without any effect on Akt, MEK1/2 and p42/44 MAPK. PD98059 abolished MEK1/2 and p42/44 MAPK activation with no effect on Akt, Raf and p38 MAPK activation. SB203580 inhibited only p38 MAPK activation by EPO. We can conclude EPO increases immediate cardioprotection through the activation of multiple signal transduction pathways.

Author List

Rafiee P, Shi Y, Su J, Pritchard KA Jr, Tweddell JS, Baker JE

Authors

John E. Baker PhD Professor in the Surgery department at Medical College of Wisconsin
Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Age Factors
Animals
Cardiotonic Agents
Erythropoietin
Interferon-Stimulated Gene Factor 3
Janus Kinase 1
Janus Kinase 2
Mitogen-Activated Protein Kinases
Myocardial Reperfusion Injury
Myocardium
Phosphatidylinositol 3-Kinases
Protein-Tyrosine Kinases
Proto-Oncogene Proteins
Rabbits
Signal Transduction
raf Kinases
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a