title: Iron homeostasis during transfusional iron overload in beta-thalassemia and sickle cell disease: changes in iron regulatory protein, hepcidin, and ferritin expression.
abstract: Hypertransfusional (>8 transfusions/year) iron in liver biopsies collected immediately after transfusions in beta-thalassemia and sickle cell disease correlated with increased expression (RNA) for iron regulatory proteins 1 and 2 (3-, 9- to 11-fold) and hepcidin RNA: (5- to 8-fold) (each p <.01), while ferritin H and L RNA remained constant. A different H:L ferritin ratio in RNA (0.03) and protein (0.2-0.6) indicated disease-specific trends and suggests novel post-transcriptional effects. Increased iron regulatory proteins could stabilize the transferrin receptor mRNA and, thereby, iron uptake. Increased hepcidin, after correction of anemia by transfusion, likely reflects excess liver iron. Finally, the absence of a detectable change in ferritin mRNA indicates insufficient oxidative stress to significantly activate MARE/ARE promoters.
authors.affiliation: Council for BioIron at CHORI, Children's Hospital Oakland Research Institute, Oakland, California 94609, USA.
authors.forename: Zandra A
authors.initials: ZA
authors.lastname: Jenkins
authors.forename: Ward
authors.initials: W
authors.lastname: Hagar
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Bowlus
authors.forename: Hans E
authors.initials: HE
authors.lastname: Johansson
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.forename: Elliott P
authors.initials: EP
authors.lastname: Vichinsky
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Theil
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications*; D023181:Antimicrobial Cationic Peptides / Q000235:genetics*; D005293:Ferritins / Q000235:genetics*; D005786:Gene Expression Regulation; D064451:Hepcidins; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000209:etiology / Q000378:metabolism*; D035941:Iron Regulatory Protein 1 / Q000235:genetics; D035942:Iron Regulatory Protein 2 / Q000235:genetics; D035925:Iron-Regulatory Proteins / Q000235:genetics*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000032:analysis; D065227:Transfusion Reaction; D017086:beta-Thalassemia / Q000150:complications*
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D035925:Iron-Regulatory Proteins; D012333:RNA, Messenger; D005293:Ferritins; D007501:Iron; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2