β Scribed by Hua Huang; Shizuo Akira; Manuela M. Santos
No coin nor oath required. For personal study only.
Under normal conditions, iron is taken up by the cells through the transferrin-mediated pathway. However, in hereditary hemochromatosis, a common iron-overloading disorder associated with mutations in the HFE gene, iron in plasma exceeds transferrin-binding capacity, and non-transferrin-bound iron (NTBI) appears in the circulation of patients with iron overload. NTBI can be taken up by hepatocytes through a transferrin-independent pathway. Lipocalin 2 (Lcn2), a secreted protein of the lipocalin family, has emerged as the mediator of an alternative, transferrin-independent pathway for cellular iron delivery. To evaluate the importance of Lcn2 in the pathogenesis of hepatic iron loading in Hfe knockout mice, we generated HfeLcn2 double-deficient mice. Our studies revealed that deletion of Lcn2 in Hfe-knockout mice does not influence hepatic iron accumulation in Hfe Ψ/Ψ mice, or their response to iron loading, as the phenotype of HfeLcn2 Ψ/Ψ mice remained indistinguishable from that of Hfe Ψ/Ψ mice. Conclusion: Lcn2 is not essential for iron delivery to hepatocytes in hemochromatosis. (HEPATOLOGY 2009;49:1012-1016.
π SIMILAR VOLUMES
Hereditary hemochromatosis (HH) is characterized by increased intestinal iron absorption that may result in iron overload. Although phlebotomy is widely practiced, it is poorly tolerated or contraindicated in patients with anemias, severe heart disease, or poor venous access, and compliance can vary