Heme oxygenase 1 is required for mammalian iron reutilization

被引:868
作者
Poss, KD
Tonegawa, S
机构
[1] Howard Hughes Medical Institute, Center for Learning and Memory, Center for Cancer Research, Cambridge
[2] Center for Cancer Research, E17-346, Massachusetts Inst. of Technology, Cambridge, MA 02139
关键词
D O I
10.1073/pnas.94.20.10919
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The majority of iron for essential mammalian biological activities such as erythropoiesis is thought to be reutilized from cellular hemoproteins, Here, we generated mice lacking functional heme oxygenase 1 (Hmox1; EC 1.14.99.3), which catabolizes heme to biliverdin, carbon monoxide, and free iron, to assess its participation in iron homeostasis, Hmox1-deficient adult mice developed an anemia associated with abnormally low serum iron levels, yet accumulated hepatic and renal iron that contributed to macromolecular oxidative damage, tissue injury, and chronic inflammation, Our results indicate that Hmox1 has an important recycling role by facilitating the release of iron from hepatic and renal cells, and describe a mouse model of human iron metabolic disorders.
引用
收藏
页码:10919 / 10924
页数:6
相关论文
共 29 条
  • [1] DECREASED CD8-P56LCK ACTIVITY IN PERIPHERAL-BLOOD T-LYMPHOCYTES FROM PATIENTS WITH HEREDITARY HEMOCHROMATOSIS
    AROSA, FA
    DASILVA, AJ
    GODINHO, IM
    TERSTEEGE, JCA
    PORTO, G
    RUDD, CE
    DESOUSA, M
    [J]. SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 1994, 39 (05) : 426 - 432
  • [2] BACON BR, 1996, HEPATOLOGY TXB LIVER, P1439
  • [3] DEGRADATION OF ENDOGENOUS HEPATIC HEME BY PATHWAYS NOT YIELDING CARBON-MONOXIDE - STUDIES IN NORMAL RAT-LIVER AND IN PRIMARY HEPATOCYTE CULTURE
    BISSELL, DM
    GUZELIAN, PS
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1980, 65 (05) : 1135 - 1140
  • [4] BOTHWELL TH, 1995, METABOLIC MOL BASES, P2237
  • [5] Bradley A., 1987, TERATOCARCINOMAS EMB, P113
  • [6] CHARACTERIZATION OF 2 HEME OXYGENASE ISOFORMS IN RAT SPLEEN - COMPARISON WITH THE HEMATIN-INDUCED AND CONSTITUTIVE ISOFORMS OF THE LIVER
    BRAGGINS, PE
    TRAKSHEL, GM
    KUTTY, RK
    MAINES, MD
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1986, 141 (02) : 528 - 533
  • [7] INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR INDUCE HEPATIC HEME OXYGENASE - FEEDBACK-REGULATION BY GLUCOCORTICOIDS
    CANTONI, L
    ROSSI, C
    RIZZARDINI, M
    GADINA, M
    GHEZZI, P
    [J]. BIOCHEMICAL JOURNAL, 1991, 279 : 891 - 894
  • [8] REGULATION OF FERRITIN AND HEME OXYGENASE SYNTHESIS IN RAT FIBROBLASTS BY DIFFERENT FORMS OF IRON
    EISENSTEIN, RS
    GARCIAMAYOL, D
    PETTINGELL, W
    MUNRO, HN
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (03) : 688 - 692
  • [9] RAPID INDUCTION OF HEME OXYGENASE-1 MESSENGER-RNA AND PROTEIN BY HYPERTHERMIA IN RAT-BRAIN - HEME OXYGENASE-2 IS NOT A HEAT-SHOCK PROTEIN
    EWING, JF
    MAINES, MD
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (12) : 5364 - 5368
  • [10] A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis
    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
    [J]. NATURE GENETICS, 1996, 13 (04) : 399 - 408