Reduced erythroid cell and erythropoietin production in response to acute anemia in prion protein-deficient (Prnp-/-) mice.
Cellular prion protein (PrPc) participates in the pathogenesis of prion diseases but its normal function remains unclear. PrPc is expressed on hematopoietic cells, including erythroid precursors. We investigated the role of PrPc in erythropoiesis in vivo with phenylhydrazine-induced acute anemia. Induction of equivalent anemia in wild-type (WT) and Prnp-/- mice resulted in a higher number of circulating reticulocytes, hematocrits and spleen weights in WT mice than in Prnp-/- mice on Days 5 and 7. Examination of bone marrow erythroid precursor cells (Ter119+) on Day 5 revealed no significant differences in the number of these cells between the two types of animals. However, a higher percentage of Ter119+ cells were going through apoptosis in Prnp-/- mice than in WT mice. Plasma erythropoietin (Epo) levels and Epo mRNA in kidneys peaked on Day 3 in response to anemia for both types of animals but rose less in Prnp-/- (5500 pg/ml ) than in WT (18,000 pg/ml) animals. Administration of recombinant human Epo to mice produced an equivalent reticulocyte response in both types of animals suggesting that the potential for erythroid generation is intact in Prnp-/- animals. These observations indicate that PrPc may modulate tissue hypoxia-sensing mechanisms or effect hypoxia target gene expression.
Zivny
Jan H
JH
1st School of Medicine, Charles University, Prague, Czech Republic.
Gelderman
Monique P
MP
Xu
Fei
F
Piper
John
J
Holada
Karel
K
Simak
Jan
J
Vostal
Jaroslav G
JG
D000208:Acute Disease; D000743:Anemia, Hemolytic / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D015672:Erythroid Precursor Cells / Q000502:physiology*; D004920:Erythropoiesis; D004921:Erythropoietin / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D016877:Oxidants / Q000494:pharmacology; D010659:Phenylhydrazines; D018621:PrPC Proteins / Q000097:blood / Q000502:physiology*; D011994:Recombinant Proteins; D012156:Reticulocytes / Q000187:drug effects / Q000502:physiology
D016877:Oxidants; D010659:Phenylhydrazines; D018621:PrPC Proteins; D011994:Recombinant Proteins; C030299:phenylhydrazine; D004921:Erythropoietin