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Erythropoietin protects cardiac myocytes against anthracycline-induced apoptosis.

Publication ,  Journal Article
Fu, P; Arcasoy, MO
Published in: Biochem Biophys Res Commun
March 9, 2007

The cardiotoxic adverse effects of anthracycline antibiotics limit their therapeutic utility as essential components of chemotherapy regimens for hematologic and solid malignancies. Here we show that the hematopoietic cytokine erythropoietin attenuates doxorubicin-induced apoptosis of primary neonatal rat ventricular cardiomyocytes in a dose-dependent manner. Erythropoietin treatment induced rapid, time-dependent phosphorylation of MAP kinases (MAPK) Erk1/2 and the phosphatidylinositol 3-kinase substrate Akt. Treatment of cardiomyocytes with inhibitors of phosphatidylinositol 3-kinase (LY294002) or Akt (Akti-1/2) abolished the protective effect of erythropoietin, whereas treatment with MAPK kinase (MEK1) inhibitor U0126 did not. Erythropoietin also induced the phosphorylation of GSK-3beta, a downstream target of PI3K-Akt. Because phosphorylation is known to inactivate GSK-3beta, we investigated whether GSK-3beta inhibition is cardioprotective. We found that GSK-3beta inhibitors SB216763 or lithium chloride blocked doxorubicin-induced cardiomyocyte apoptosis in a manner similar to erythropoietin, suggesting that GSK-3beta inhibition is involved in erythropoietin-mediated cardioprotection. Erythropoietin may serve as a novel cardioprotective agent against anthracycline-induced cardiotoxicity.

Duke Scholars

Published In

Biochem Biophys Res Commun

DOI

ISSN

0006-291X

Publication Date

March 9, 2007

Volume

354

Issue

2

Start / End Page

372 / 378

Location

United States

Related Subject Headings

  • Rats, Sprague-Dawley
  • Rats
  • Myocytes, Cardiac
  • Erythropoietin
  • Doxorubicin
  • Dose-Response Relationship, Drug
  • Cells, Cultured
  • Biochemistry & Molecular Biology
  • Apoptosis
  • Antibiotics, Antineoplastic
 

Citation

APA
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ICMJE
MLA
NLM
Fu, P., & Arcasoy, M. O. (2007). Erythropoietin protects cardiac myocytes against anthracycline-induced apoptosis. Biochem Biophys Res Commun, 354(2), 372–378. https://doi.org/10.1016/j.bbrc.2007.01.044
Fu, Ping, and Murat O. Arcasoy. “Erythropoietin protects cardiac myocytes against anthracycline-induced apoptosis.Biochem Biophys Res Commun 354, no. 2 (March 9, 2007): 372–78. https://doi.org/10.1016/j.bbrc.2007.01.044.
Fu P, Arcasoy MO. Erythropoietin protects cardiac myocytes against anthracycline-induced apoptosis. Biochem Biophys Res Commun. 2007 Mar 9;354(2):372–8.
Fu, Ping, and Murat O. Arcasoy. “Erythropoietin protects cardiac myocytes against anthracycline-induced apoptosis.Biochem Biophys Res Commun, vol. 354, no. 2, Mar. 2007, pp. 372–78. Pubmed, doi:10.1016/j.bbrc.2007.01.044.
Fu P, Arcasoy MO. Erythropoietin protects cardiac myocytes against anthracycline-induced apoptosis. Biochem Biophys Res Commun. 2007 Mar 9;354(2):372–378.
Journal cover image

Published In

Biochem Biophys Res Commun

DOI

ISSN

0006-291X

Publication Date

March 9, 2007

Volume

354

Issue

2

Start / End Page

372 / 378

Location

United States

Related Subject Headings

  • Rats, Sprague-Dawley
  • Rats
  • Myocytes, Cardiac
  • Erythropoietin
  • Doxorubicin
  • Dose-Response Relationship, Drug
  • Cells, Cultured
  • Biochemistry & Molecular Biology
  • Apoptosis
  • Antibiotics, Antineoplastic