title: Haemolytic anaemia and alterations in hepatic iron metabolism in aged mice lacking Cu,Zn-superoxide dismutase.
abstract: The continuous recycling of haem iron following phagocytosis and catabolism of senescent and damaged red blood cells by macrophages is a crucial process in the maintenance of systemic iron homoeostasis. However, little is known about macrophage iron handling in haemolytic states resulting from a deficiency in antioxidant defences. Our observations indicate that the recently described chronic, but moderate regenerative, haemolytic anaemia of aged SOD1 (superoxide dismutase 1)-knockout mice is associated with red blood cell modifications and sensitivity to both intra- and extra-vascular haemolysis. In the present study, we have characterized the molecular pathways of iron turnover in the liver of Sod1-deficient mice. Despite iron accumulation in liver macrophages, namely Kupffer cells, we did not measure any significant change in non-haem liver iron. Interestingly, in Kupffer cells, expression of the rate-limiting enzyme in haem degradation, haem oxygenase-1, and expression of the iron exporter ferroportin were both up-regulated, whereas the hepcidin mRNA level in the liver was decreased in Sod1-/- mice. These results suggest that concerted changes in the hepatic expression of iron- and haem-related genes in response to haemolytic anaemia in Sod1-/- mice act to reduce toxic iron accumulation in the liver and respond to the needs of erythropoiesis.
authors.affiliation: Department of Molecular Biology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzebiec, Wolka Kosowska, Poland.
authors.forename: Rafał R
authors.initials: RR
authors.lastname: Starzyński
authors.forename: François
authors.initials: F
authors.lastname: Canonne-Hergaux
authors.forename: Alexandra
authors.initials: A
authors.lastname: Willemetz
authors.forename: Mikołaj A
authors.initials: MA
authors.lastname: Gralak
authors.forename: Jarosław
authors.initials: J
authors.lastname: Woliński
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Styś
authors.forename: Jarosław
authors.initials: J
authors.lastname: Olszak
authors.forename: Paweł
authors.initials: P
authors.lastname: Lipiński
mesh_terms: D000375:Aging; D000743:Anemia, Hemolytic / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006418:Heme / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis; D064451:Hepcidins; D007501:Iron / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000235:genetics; D000098742:Ferroportin
chemical_list: D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; C579599:Hamp protein, mouse; D006454:Hemoglobins; D064451:Hepcidins; D012333:RNA, Messenger; D000098742:Ferroportin; D006418:Heme; D007501:Iron; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase