Erythropoietin protects myocardin-expressing cardiac stem cells against cytotoxicity of tumor necrosis factor-alpha.
Cardiac stem cells are vulnerable to inflammation caused by infarction or ischemic injury. The growth factor, erythropoietin (Epo), ameliorates the inflammatory response of the myocardium to ischemic injury. This study was designed to assess the role of Epo in regulation of expression and activation of the cell death-associated intracellular signaling components in cardiac myoblasts stimulated with the proinflammatory cytokine tumor necrosis factor (TNF)-alpha. Cardiac myoblasts isolated from canine embryonic hearts characterized by expression of myocardin A, a promyogenic transcription factor for cardiovascular muscle development were pretreated with Epo and then exposed to TNF-alpha. Compared to untreated cells, the Epo-treated cardiac myoblasts exhibited better morphology and viability. Immunoblotting revealed lower levels of active caspase-3 and reductions in iNOS expression and NO production in Epo-treated cells. Furthermore, Epo pretreatment reduced nuclear translocation of NF-kappaB and inhibited phosphorylation of inhibitor of kappa B (IkappaB) in TNF-alpha-stimulated cardiac myoblasts. Thus, Epo protects cardiac myocyte progenitors or myoblasts against the cytotoxic effects of TNF-alpha by inhibiting NF-kappaB-mediated iNOS expression and NO production and by preventing caspase-3 activation.
Madonna
Rosalinda
R
The Center for Cardiovascular Biology and Atherosclerosis Research, The University of Texas Health Science Center, Houston, Texas, USA.
Shelat
Harnath
H
Xue
Qun
Q
Willerson
James T
JT
De Caterina
Raffaele
R
Geng
Yong-Jian
YJ
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D018929:Cell Culture Techniques; D016923:Cell Death; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects*; D004285:Dogs; D004921:Erythropoietin / Q000494:pharmacology*; D005434:Flow Cytometry; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009573:Nitrites / Q000378:metabolism; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*; D000099251:Myocardin
D053148:Caspase 3; D004921:Erythropoietin; D009573:Nitrites; D009687:Nuclear Proteins; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D000099251:Myocardin