Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin.
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.
Robach
Paul
P
Département Médical, Ecole Nationale de Ski et d'Alpinisme, Chamonix, France.
Recalcati
Stefania
S
Girelli
Domenico
D
Gelfi
Cecilia
C
Aachmann-Andersen
Niels J
NJ
Thomsen
Jonas J
JJ
Norgaard
Anne M
AM
Alberghini
Alessandra
A
Campostrini
Natascia
N
Castagna
Annalisa
A
Viganò
Agnese
A
Santambrogio
Paolo
P
Kempf
Tibor
T
Wollert
Kai C
KC
Moutereau
Stéphane
S
Lundby
Carsten
C
Cairo
Gaetano
G
D000328:Adult; D015703:Antigens, CD / Q000235:genetics; D023181:Antimicrobial Cationic Peptides / Q000032:analysis / Q000096:biosynthesis; D001706:Biopsy; D027682:Cation Transport Proteins / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D004911:Erythrocyte Volume / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009211:Myoglobin / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D011990:Receptors, Transferrin / Q000235:genetics; D011994:Recombinant Proteins; D055815:Young Adult; D000098742:Ferroportin
D015703:Antigens, CD; D023181:Antimicrobial Cationic Peptides; C068126:CD71 antigen; D027682:Cation Transport Proteins; C578702:HAMP protein, human; D006454:Hemoglobins; D064451:Hepcidins; D009211:Myoglobin; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D011994:Recombinant Proteins; C103998:epoetin beta; D000098742:Ferroportin; D004921:Erythropoietin; D007501:Iron