Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin.

Abstract

The high iron demand associated with enhanced erythropoiesis during high-altitude hypoxia leads to skeletal muscle iron mobilization and decrease in myoglobin protein levels. To investigate the effect of enhanced erythropoiesis on systemic and muscle iron metabolism under nonhypoxic conditions, 8 healthy volunteers were treated with recombinant erythropoietin (rhEpo) for 1 month. As expected, the treatment efficiently increased erythropoiesis and stimulated bone marrow iron use. It was also associated with a prompt and considerable decrease in urinary hepcidin and a slight transient increase in GDF-15. The increased iron use and reduced hepcidin levels suggested increased iron mobilization, but the treatment was associated with increased muscle iron and L ferritin levels. The muscle expression of transferrin receptor and ferroportin was up-regulated by rhEpo administration, whereas no appreciable change in myoglobin levels was observed, which suggests unaltered muscle oxygen homeostasis. In conclusion, under rhEpo stimulation, the changes in the expression of muscle iron proteins indicate the occurrence of skeletal muscle iron accumulation despite the remarkable hepcidin suppression that may be mediated by several factors, such as rhEpo or decreased transferrin saturation or both.

• Authors: Paul Robach, Stefania Recalcati, Domenico Girelli, Cecilia Gelfi, Niels J Aachmann-Andersen, Jonas J Thomsen, Anne M Norgaard, Alessandra Alberghini, Natascia Campostrini, Annalisa Castagna, Agnese Viganò, Paolo Santambrogio, Tibor Kempf, Kai C Wollert, Stéphane Moutereau, Carsten Lundby, Gaetano Cairo
• Journal: Blood (Blood) Vol. 113 Issue 26 Pg. 6707-15 (Jun 25 2009) ISSN: 1528-0020 [Electronic] United States
• PMID: 19264680 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Antimicrobial Cationic Peptides
• CD71 antigen
• Cation Transport Proteins
• HAMP protein, human
• Hemoglobins
• Hepcidins
• Myoglobin
• RNA, Messenger
• Receptors, Transferrin
• Recombinant Proteins
• epoetin beta
• metal transporting protein 1
• Erythropoietin
• Iron

Topics

• Adult
• Antigens, CD (genetics)
• Antimicrobial Cationic Peptides (analysis, biosynthesis)
• Biopsy
• Cation Transport Proteins (genetics)
• Down-Regulation (drug effects)
• Erythrocyte Volume (drug effects)
• Erythropoiesis (drug effects)
• Erythropoietin (administration & dosage, pharmacology)
• Hematocrit
• Hemoglobins (analysis)
• Hepcidins
• Humans
• Iron (metabolism)
• Male
• Muscle, Skeletal (cytology, drug effects, metabolism)
• Myoglobin (analysis)
• RNA, Messenger (analysis)
• Receptors, Transferrin (genetics)
• Recombinant Proteins
• Young Adult