Document Detail


Erythropoietin (EPO) affords more potent cardioprotection by activation of distinct signaling to mitochondrial kinases compared with carbamylated EPO.
MedLine Citation:
PMID:  20953685     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Erythropoietin (EPO) and its non-erythrogenic derivative, carbarmylated EPO (CEPO), have been reported to activate different receptors (homomeric EPO receptor vs. heteromeric receptor consisting of EPO receptor monomer and common β-subunit). The aim of this study was to examine differences between EPO and CEPO in efficacy of cardioprotection against infarction and in activation of pro-survival kinases.
METHODS: In isolated rat hearts, infarction was induced by global ischemia followed by reperfusion. Infarct size was determined 2 h after reperfusion, and ventricular tissues for immunoblotting were sampled at 5 min after reperfusion.
RESULTS: Pretreatment with EPO (10 units/ml) before ischemia reduced infarct size (% of risk area; %IS/AR) from 47.0 ± 2.1% of the control after 20-min ischemia to 24.7 ± 4.3% and from 62.0 ± 3.0% after 25-min ischemia to 45.5 ± 4.1%. Desialylated EPO (asialoEPO, 100 ng/ml) mimicked the protection by EPO. However, CEPO (100 ng/ml) failed to reduce infarct size after 20-min ischemia (%IS/AR = 47.5 ± 5.9%) and that after 25-min ischemia (%IS/AR = 56.1 ± 4.2%). The infarct size-limiting effect of CEPO was not shown either by increasing CEPO dose to 500 ng/ml or by shortening ischemia to 15 min. Both EPO and CEPO enhanced phosphorylation of cytosolic GSK-3β upon reperfusion. In contrast, phosphorylation of GSK-3β, Akt, and PKC-ε in mitochondria upon reperfusion was significantly enhanced by EPO but not by CEPO.
CONCLUSION: EPO affords more potent protection against infarction than does CEPO by distinct activation of signaling leading to phosphorylation of pro-survival protein kinases in mitochondria upon reperfusion.
Authors:
Takahiro Sato; Masaya Tanno; Takayuki Miki; Toshiyuki Yano; Tatsuya Sato; Kazuaki Shimamoto; Tetsuji Miura
Related Documents :
2907055 - Effects of glutamic acid on cardiac function and energy metabolism of rat heart during ...
14655995 - Modified two-step model for studying the inflammatory response during myocardial ischem...
15597015 - Minimally invasive close-chest method for creating reperfused or occlusive myocardial i...
11687725 - Is peripheral blood a reliable indicator of acute oxidative stress following heart isch...
20067385 - Adenylate-cyclase vi transforms ventricular cardiomyocytes into biological pacemaker ce...
12423705 - Nephropathy requiring dialysis after percutaneous coronary intervention and the critica...
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy     Volume:  24     ISSN:  1573-7241     ISO Abbreviation:  Cardiovasc Drugs Ther     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2011-03-09     Completed Date:  2011-07-07     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  8712220     Medline TA:  Cardiovasc Drugs Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  401-8     Citation Subset:  IM    
Affiliation:
Division of Cardiology, Second Department of Internal Medicine, Sapporo Medical University School of Medicine, South-1 West-16, Chuo-ku, Sapporo, 060-8543, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Cardiotonic Agents / pharmacology*
Erythropoietin / analogs & derivatives*,  pharmacology*
Extracellular Signal-Regulated MAP Kinases
Glycogen Synthase Kinase 3 / metabolism
Male
Mitochondria / drug effects,  enzymology*
Myocardial Infarction / enzymology,  prevention & control*
Myocardial Reperfusion Injury / drug therapy*,  enzymology
Phosphorylation / drug effects
Protein Kinase C-epsilon / metabolism
Protein Kinases / metabolism*
Proto-Oncogene Proteins c-akt / metabolism
Rats
Rats, Sprague-Dawley
Receptors, Erythropoietin / metabolism
Signal Transduction / drug effects
Chemical
Reg. No./Substance:
0/Cardiotonic Agents; 0/Receptors, Erythropoietin; 0/carbamylated erythropoietin; 11096-26-7/Erythropoietin; EC 2.7.-/Protein Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.13/Protein Kinase C-epsilon; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.26/Glycogen Synthase Kinase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Efficacy and Safety of Rosuvastatin 5 mg in Combination with Fenofibric Acid 135 mg in Patients wi...
Next Document:  Compositionality of arm movements can be realized by propagating synchrony.