title: Erythropoietin protects cardiomyocytes from cell death during hypoxia/reperfusion injury through activation of survival signaling pathways.
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.
authors.affiliation: Centre for Biotechnology, Anna University, Chennai, Tamil Nadu, India.
authors.forename: Asiya  A
authors.initials: A
authors.lastname: Parvin
authors.affiliation: Centre for Biotechnology, Anna University, Chennai, Tamil Nadu, India.
authors.forename: Raj  A
authors.initials: R
authors.lastname: Pranap
authors.affiliation: Centre for Biotechnology, Anna University, Chennai, Tamil Nadu, India.
authors.forename: U
authors.initials: U
authors.lastname: Shalini
authors.affiliation: Centre for Biotechnology, Anna University, Chennai, Tamil Nadu, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Devendran
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: John E
authors.initials: JE
authors.lastname: Baker
authors.affiliation: Centre for Biotechnology, Anna University, Chennai, Tamil Nadu, India.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Dhanasekaran
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D004921:Erythropoietin / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020011:Protective Agents; D017382:Reactive Oxygen Species; D004921:Erythropoietin; D053148:Caspase 3