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Erythropoietin protects cardiomyocytes from cell death during hypoxia/reperfusion injury through activation of survival signaling pathways. PLoS One 2014;9(9):e107453

Date

09/23/2014

Pubmed ID

25237819

Pubmed Central ID

PMC4169563

DOI

10.1371/journal.pone.0107453

Scopus ID

2-s2.0-84907202527   22 Citations

Abstract

Hypoxia/Reoxygenation (H/R) cardiac injury is of great importance in understanding Myocardial Infarctions, which affect a major part of the working population causing debilitating side effects and often-premature mortality. H/R injury primarily consists of apoptotic and necrotic death of cardiomyocytes due to a compromise in the integrity of the mitochondrial membrane. Major factors associated in the deregulation of the membrane include fluctuating reactive oxygen species (ROS), deregulation of mitochondrial permeability transport pore (MPTP), uncontrolled calcium (Ca2+) fluxes, and abnormal caspase-3 activity. Erythropoietin (EPO) is strongly inferred to be cardioprotective and acts by inhibiting the above-mentioned processes. Surprisingly, the underlying mechanism of EPO's action and H/R injury is yet to be fully investigated and elucidated. This study examined whether EPO maintains Ca2+ homeostasis and the mitochondrial membrane potential (ΔΨm) in cardiomyocytes when subjected to H/R injury and further explored the underlying mechanisms involved. H9C2 cells were exposed to different concentrations of EPO post-H/R, and 20 U/ml EPO was found to significantly increase cell viability by inhibiting the intracellular production of ROS and caspase-3 activity. The protective effect of EPO was abolished when H/R-induced H9C2 cells were treated with Wortmannin, an inhibitor of Akt, suggesting the mechanism of action through the activation Akt, a major survival pathway.

Author List

Parvin A, Pranap R, Shalini U, Devendran A, Baker JE, Dhanasekaran A

Author

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




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

Animals
Caspase 3
Cell Hypoxia
Cell Line
Erythropoietin
Membrane Potential, Mitochondrial
Protective Agents
Rats
Reactive Oxygen Species
Reperfusion Injury
Signal Transduction
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a