Hemolytic anemia and alterations in hepatic iron metabolism in aged mice lacking Cu,Zn-superoxide dismutase - Archive ouverte HAL
Article Dans Une Revue Biochemical Journal Année : 2009

Hemolytic anemia and alterations in hepatic iron metabolism in aged mice lacking Cu,Zn-superoxide dismutase

Rafał Radoslaw Starzyński
  • Fonction : Auteur
François Canonne-Hergaux
Alexandra Willemetz
  • Fonction : Auteur
Mikołaj Antoni Gralak
  • Fonction : Auteur
Jarosław Woliński
  • Fonction : Auteur
Agnieszka Styś
  • Fonction : Auteur
Jarosław Olszak
  • Fonction : Auteur

Résumé

The continuous recycling of heme iron following phagocytosis and catabolism of senescent and damaged red blood cells by macrophages is a crucial process in the maintenance of systemic iron homeostasis. However, little is known about macrophage iron handling in hemolytic states resulting from a deficiency in antioxidant defenses. Our observations indicate that recently described [Iuchi Y, Okada F, Onuma K, Onoda T, Asao H, Kobayashi M, Fuji J. Biochem. J. (2007) 402, 219-227] the chronic but moderate regenerative hemolytic anemia of old superoxide dismutase 1 (SOD1) knockout mice is associated with red blood cells modifications and sensitivity to both intra- and extravascular hemolysis. We have then 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-heme liver iron. Interestingly in Kupffer cells, expression of the rate-limiting enzyme in heme degradation, the heme oxygenase-1 and expression of the iron exporter ferroportin were both upregulated whereas hepcidin mRNA level in the liver was decreased in SOD1–/– mice. These results suggest that concerted changes in the hepatic expression of iron- and heme-related genes in response to hemolytic anemia in SOD1–/– mice act to reduce toxic iron accumulation in the liver and respond to the needs of erythropoiesis.

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Dates et versions

hal-00479120 , version 1 (30-04-2010)

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Rafał Radoslaw Starzyński, François Canonne-Hergaux, Alexandra Willemetz, Mikołaj Antoni Gralak, Jarosław Woliński, et al.. Hemolytic anemia and alterations in hepatic iron metabolism in aged mice lacking Cu,Zn-superoxide dismutase. Biochemical Journal, 2009, 420 (3), pp.383-390. ⟨10.1042/BJ20082137⟩. ⟨hal-00479120⟩

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