Haemolytic anaemia 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

Haemolytic anaemia and alterations in hepatic iron metabolism in aged mice lacking Cu,Zn-superoxide dismutase.

Rafał R Starzyński
  • Fonction : Auteur
Mikołaj A Gralak
  • Fonction : Auteur
Jarosław Woliński
  • Fonction : Auteur
Agnieszka Styś
  • Fonction : Auteur
Jarosław Olszak
  • Fonction : Auteur
Paweł Lipiński
  • Fonction : Auteur

Résumé

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.
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Dates et versions

hal-00439841 , version 1 (08-12-2009)

Identifiants

Citer

Rafał R Starzyński, François Canonne-Hergaux, Alexandra Willemetz, Mikołaj A Gralak, Jarosław Woliński, et al.. Haemolytic anaemia and alterations in hepatic iron metabolism in aged mice lacking Cu,Zn-superoxide dismutase.. Biochemical Journal, 2009, 420 (3), pp.383-90. ⟨10.1042/BJ20082137⟩. ⟨hal-00439841⟩
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