Expression of ferroportin in hemochromatosis liver

被引:12
作者
Adams, PC
Barbin, YP
Khan, ZA
Chakrabarti, S
机构
[1] Univ Western Ontario, London Hlth Sci Ctr, Dept Med, London, ON N6A 5A5, Canada
[2] Univ Western Ontario, London Hlth Sci Ctr, Dept Pathol, London, ON N6A 5A5, Canada
关键词
D O I
10.1016/S1079-9796(03)00136-0
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Iron-regulated transporter protein 1 (IREG1 or ferroportin 1) is a transmembrane iron transporter that has been described in macrophages and hepatocytes. Ferroportin mutations have been described to result in hepatic iron overload in human pedigrees. The role of hepatic ferroportin in the pathogenesis of C282Y-linked hernochromatosis has not been clearly established. The objective was to study the expression of ferroportin mRNA and protein in C282Y-linked hemochromatosis liver and in controls. Human liver biopsies were stained with an anti-ferroportin antibody and quantitation of ferroportin at 62 kDa was done by Western blotting. mRNA was studied by real time RT-PCR. Ferroportin protein expression was increased in C282Y homozygotes (n = 23) compared to wild-type patients (n = 37) (P < 0.003). There was no significant correlation between ferroportin protein or mRNA expression (n = 25) and liver iron concentration or serum ferritin. Immunohistochemical staining demonstrated ferroportin in hepatocytes and macrophages. In conclusion, ferroportin protein is increased in iron-loaded hemochromatosis liver. The increase in ferroportin protein without an increase in mRNA is consistent with iron-mediated translational regulation through the 5'IRE in the mRNA. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:256 / 261
页数:6
相关论文
共 20 条
[1]   A novel mammalian iron-regulated protein involved in intracellular iron metabolism [J].
Abboud, S ;
Haile, DJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (26) :19906-19912
[2]   Genotypic/phenotypic correlations in genetic hemochromatosis: Evolution of diagnostic criteria [J].
Adams, PC ;
Chakrabarti, S .
GASTROENTEROLOGY, 1998, 114 (02) :319-323
[3]   Medical progress: Disorders of iron metabolism [J].
Andrews, NC .
NEW ENGLAND JOURNAL OF MEDICINE, 1999, 341 (26) :1986-1995
[4]   Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis [J].
Bridle, KR ;
Frazer, DM ;
Wilkins, SJ ;
Dixon, JL ;
Purdie, DM ;
Crawford, DHG ;
Subramaniam, VN ;
Powell, LW ;
Anderson, GJ ;
Ramm, GA .
LANCET, 2003, 361 (9358) :669-673
[5]  
CAIRO G, 1994, J BIOL CHEM, V269, P6405
[6]   The hemochromatosis protein HFE inhibits iron export from macrophages [J].
Drakesmith, H ;
Sweetland, E ;
Schimanski, L ;
Edwards, J ;
Cowley, D ;
Ashraf, M ;
Bastin, J ;
Townsend, ARM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (24) :15602-15607
[7]   A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis [J].
Feder, JN ;
Gnirke, A ;
Thomas, W ;
Tsuchihashi, Z ;
Ruddy, DA ;
Basava, A ;
Dormishian, F ;
Domingo, R ;
Ellis, MC ;
Fullan, A ;
Hinton, LM ;
Jones, NL ;
Kimmel, BE ;
Kronmal, GS ;
Lauer, P ;
Lee, VK ;
Loeb, DB ;
Mapa, FA ;
McClelland, E ;
Meyer, NC ;
Mintier, GA ;
Moeller, N ;
Moore, T ;
Morikang, E ;
Prass, CE ;
Quintana, L ;
Starnes, SM ;
Schatzman, RC ;
Brunke, KJ ;
Drayna, DT ;
Risch, NJ ;
Bacon, BR ;
Wolff, RK .
NATURE GENETICS, 1996, 13 (04) :399-408
[8]   Expression of hepcidin in hereditary hemochromatosis: evidence for a regulation in response to the serum transferrin saturation and to non-transferrin-bound iron [J].
Gehrke, SG ;
Kulaksiz, H ;
Herrmann, T ;
Riedel, HD ;
Bents, K ;
Veltkamp, C ;
Stremmel, W .
BLOOD, 2003, 102 (01) :371-376
[9]   BILIARY-EXCRETION OF IRON AND FERRITIN IN IDIOPATHIC HEMOCHROMATOSIS [J].
HULTCRANTZ, R ;
ANGELIN, B ;
BJORNRASMUSSEN, E ;
EWERTH, S ;
EINARSSON, K .
GASTROENTEROLOGY, 1989, 96 (06) :1539-1545
[10]   Polymorphism in intron 4 of HFE may cause overestimation of C282Y homozygote prevalence in haemochromatosis [J].
Jeffrey, GP ;
Chakrabarti, S ;
Hegele, RA ;
Adams, PC .
NATURE GENETICS, 1999, 22 (04) :325-326