Deficiency of heme-regulated eIF2alpha kinase decreases hepcidin expression and splenic iron in HFE-/- mice.
Heme-regulated eIF2alpha kinase (HRI) is essential for regulating globin translation in iron deficiency and in beta-thalassemia. We investigated the role of heme-regulated eIF2alpha kinase in hemoglobin and red blood cell production as well as in iron homeostasis in a mouse model of iron overload. We show that HRI deficiency does not significantly affect red cell parameters of hemochromatosis (HFE(-)(/)(-)) mice. Importantly, heme-regulated eIF2alpha kinase deficiency exacerbates decreases in hepcidin expression and splenic macrophage iron in HFE(-)(/)(-) mice. Furthermore, the serum level of bone morphogenic protein 2, which positively regulates hepcidin, is reduced in heme-regulated eIF2alpha kinase deficiency, but not in HFE deficiency.
Liu
Sijin
S
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Suragani
Rajasekhar N V S
RN
Han
Anping
A
Zhao
Wanting
W
Andrews
Nancy C
NC
Chen
Jane-Jane
JJ
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005838:Genotype; D006418:Heme / Q000737:chemistry*; D006432:Hemochromatosis / Q000235:genetics*; D064451:Hepcidins; D007501:Iron / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D019892:eIF-2 Kinase / Q000378:metabolism*
D023181:Antimicrobial Cationic Peptides; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; C579599:Hamp protein, mouse; D064451:Hepcidins; D016212:Transforming Growth Factor beta; D006418:Heme; D007501:Iron; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; C531557:eIF2alpha kinase, mouse