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Erythropoietin activates mitochondrial biogenesis and couples red cell mass to mitochondrial mass in the heart.

Publication ,  Journal Article
Carraway, MS; Suliman, HB; Jones, WS; Chen, C-W; Babiker, A; Piantadosi, CA
Published in: Circ Res
June 11, 2010

RATIONALE: Erythropoietin (EPO) is often administered to cardiac patients with anemia, particularly from chronic kidney disease, and stimulation of erythropoiesis may stabilize left ventricular and renal function by recruiting protective effects beyond the correction of anemia. OBJECTIVE: We examined the hypothesis that EPO receptor (EpoR) ligand-binding, which activates endothelial NO synthase (eNOS), regulates the prosurvival program of mitochondrial biogenesis in the heart. METHODS AND RESULTS: We investigated the effects of EPO on mitochondrial biogenesis over 14 days in healthy mice. Mice expressing a mitochondrial green fluorescent protein reporter construct demonstrated sharp increases in myocardial mitochondrial density after 3 days of EPO administration that peaked at 7 days and surpassed hepatic or renal effects and anteceded significant increases in blood hemoglobin content. Quantitatively, in wild-type mice, complex II activity, state 3 respiration, and mtDNA copy number increased significantly; also, resting energy expenditure and natural running speed improved, with no evidence of an increase in left ventricular mass index. Mechanistically, EPO activated cardiac mitochondrial biogenesis by enhancement of nuclear respiratory factor-1, PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator 1alpha), and mitochondrial transcription factor-A gene expression in wild-type but not in eNOS(-/-) or protein kinase B (Akt1)(-/-) mice. EpoR was required, because EpoR silencing in cardiomyocytes blocked EPO-mediated nuclear translocation of nuclear respiratory factor-1. CONCLUSIONS: These findings support a new physiological and protective role for EPO, acting through its cell surface receptor and eNOS-Akt1 signal transduction, in matching cardiac mitochondrial mass to the convective O(2) transport capacity as erythrocyte mass expands.

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Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

June 11, 2010

Volume

106

Issue

11

Start / End Page

1722 / 1730

Location

United States

Related Subject Headings

  • Transcription Factors
  • Trans-Activators
  • Time Factors
  • Signal Transduction
  • Recombinant Proteins
  • Receptors, Erythropoietin
  • RNA Interference
  • Proto-Oncogene Proteins c-akt
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Nuclear Respiratory Factor 1
 

Citation

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Carraway, M. S., Suliman, H. B., Jones, W. S., Chen, C.-W., Babiker, A., & Piantadosi, C. A. (2010). Erythropoietin activates mitochondrial biogenesis and couples red cell mass to mitochondrial mass in the heart. Circ Res, 106(11), 1722–1730. https://doi.org/10.1161/CIRCRESAHA.109.214353
Carraway, Martha S., Hagir B. Suliman, W Schuyler Jones, Chien-Wen Chen, Abdelwahid Babiker, and Claude A. Piantadosi. “Erythropoietin activates mitochondrial biogenesis and couples red cell mass to mitochondrial mass in the heart.Circ Res 106, no. 11 (June 11, 2010): 1722–30. https://doi.org/10.1161/CIRCRESAHA.109.214353.
Carraway MS, Suliman HB, Jones WS, Chen C-W, Babiker A, Piantadosi CA. Erythropoietin activates mitochondrial biogenesis and couples red cell mass to mitochondrial mass in the heart. Circ Res. 2010 Jun 11;106(11):1722–30.
Carraway, Martha S., et al. “Erythropoietin activates mitochondrial biogenesis and couples red cell mass to mitochondrial mass in the heart.Circ Res, vol. 106, no. 11, June 2010, pp. 1722–30. Pubmed, doi:10.1161/CIRCRESAHA.109.214353.
Carraway MS, Suliman HB, Jones WS, Chen C-W, Babiker A, Piantadosi CA. Erythropoietin activates mitochondrial biogenesis and couples red cell mass to mitochondrial mass in the heart. Circ Res. 2010 Jun 11;106(11):1722–1730.

Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

June 11, 2010

Volume

106

Issue

11

Start / End Page

1722 / 1730

Location

United States

Related Subject Headings

  • Transcription Factors
  • Trans-Activators
  • Time Factors
  • Signal Transduction
  • Recombinant Proteins
  • Receptors, Erythropoietin
  • RNA Interference
  • Proto-Oncogene Proteins c-akt
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Nuclear Respiratory Factor 1