Erythropoietin protects myocardin-expressing cardiac stem cells against cytotoxicity of tumor necrosis factor-{alpha}

Journal Article · Thu Oct 15 04:00:00 EDT 2009 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2009.07.016· OSTI ID:22209827

Madonna, Rosalinda ^[1]; Shelat, Harnath; Xue, Qun; Willerson, James T. ^[1]; De Caterina, Raffaele ^[2]; Geng, Yong-Jian ^[1]

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1. The Center for Cardiovascular Biology and Atherosclerosis Research, The University of Texas Health Science Center at Houston, Texas (United States)
2. Institute of Cardiology, and Center of Excellence on Aging, 'G. d'Annunzio' University, Chieti (Italy)

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-{kappa}B and inhibited phosphorylation of inhibitor of kappa B (I{kappa}B) in TNF-{alpha}-stimulated cardiac myoblasts. Thus, Epo protects cardiac myocyte progenitors or myoblasts against the cytotoxic effects of TNF-{alpha} by inhibiting NF-{kappa}B-mediated iNOS expression and NO production and by preventing caspase-3 activation.

• OSTI ID: 22209827
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 17 Vol. 315; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
DOGS
ERYTHROPOIETIN
GROWTH FACTORS
INFLAMMATION
INJURIES
ISCHEMIA
MYOBLASTS
MYOCARDIUM
NITRIC OXIDE
PHOSPHORYLATION
STEM CELLS
TOXICITY
TRANSCRIPTION FACTORS