Limited iron export by hepatocytes contributes to hepatic iron-loading in the Hfe knockout mouse

Anita Chua, S.F. Drake, C.E. Herbison, John Olynyk, Peter Leedman, Debbie Trinder

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    13 Citations (Scopus)

    Abstract

    Background/Aims: In hereditary hemochromatosis, iron-loading of hepatocytes is associated with increased iron uptake while little is known about iron release. This study aims to characterise iron release and ferroportin expression by Hfe knockout hepatocytes to determine if they contribute to iron overload in haemochromatosis.Methods: Iron release by hepatocytes from Hfe knockout, non-iron-loaded and iron-loaded wild-type mice was measured after incubation with nontransferrin-bound iron as iron-citrate.Results: Iron release and ferroportin expression by hepatocytes from Hfe knockout, non-iron-loaded and in vivo iron-loaded wild-type mice were similar although, nontransferrin-bound iron uptake was significantly increased in Hfe knockout hepatocytes and decreased in iron-loaded wild-type hepatocytes compared with non-iron-loaded wild-type cells. When expressed as a percentage of total iron uptake, iron release was decreased in Hfe knockout hepatocytes (4.6 +/- 0.7 versus 13.7 +/- 1.2%, P < 0.0001) and increased in iron-loaded wild-type hepatocytes (29.5 +/- 0.5 versus 13.5 +/- 0.7%; P < 0.0001) compared with wild-type hepatocytes. In contrast, in vitro iron-loading increased iron release and ferroportin expression by both Hfe knockout and wild-type hepatocytes.Conclusions: Hfe knockout hepatocytes accumulate iron as a result of limited iron export and enhanced iron uptake. The correlation between iron release and ferroportin expression suggests that iron export in hepatocytes is mediated by ferroportin. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
    Original languageEnglish
    Pages (from-to)176-182
    JournalJournal of Hepatology
    Volume44
    Issue number1
    DOIs
    Publication statusPublished - 2006

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    Knockout Mice
    Hepatocytes
    Iron
    Liver
    Hemochromatosis
    Iron Overload

    Cite this

    @article{ce4a72ab416b4db38433888c86c079ed,
    title = "Limited iron export by hepatocytes contributes to hepatic iron-loading in the Hfe knockout mouse",
    abstract = "Background/Aims: In hereditary hemochromatosis, iron-loading of hepatocytes is associated with increased iron uptake while little is known about iron release. This study aims to characterise iron release and ferroportin expression by Hfe knockout hepatocytes to determine if they contribute to iron overload in haemochromatosis.Methods: Iron release by hepatocytes from Hfe knockout, non-iron-loaded and iron-loaded wild-type mice was measured after incubation with nontransferrin-bound iron as iron-citrate.Results: Iron release and ferroportin expression by hepatocytes from Hfe knockout, non-iron-loaded and in vivo iron-loaded wild-type mice were similar although, nontransferrin-bound iron uptake was significantly increased in Hfe knockout hepatocytes and decreased in iron-loaded wild-type hepatocytes compared with non-iron-loaded wild-type cells. When expressed as a percentage of total iron uptake, iron release was decreased in Hfe knockout hepatocytes (4.6 +/- 0.7 versus 13.7 +/- 1.2{\%}, P < 0.0001) and increased in iron-loaded wild-type hepatocytes (29.5 +/- 0.5 versus 13.5 +/- 0.7{\%}; P < 0.0001) compared with wild-type hepatocytes. In contrast, in vitro iron-loading increased iron release and ferroportin expression by both Hfe knockout and wild-type hepatocytes.Conclusions: Hfe knockout hepatocytes accumulate iron as a result of limited iron export and enhanced iron uptake. The correlation between iron release and ferroportin expression suggests that iron export in hepatocytes is mediated by ferroportin. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",
    author = "Anita Chua and S.F. Drake and C.E. Herbison and John Olynyk and Peter Leedman and Debbie Trinder",
    year = "2006",
    doi = "10.1016/j.jhep.2005.08.012",
    language = "English",
    volume = "44",
    pages = "176--182",
    journal = "Journal of Hepatology",
    issn = "0168-8278",
    publisher = "Pergamon",
    number = "1",

    }

    Limited iron export by hepatocytes contributes to hepatic iron-loading in the Hfe knockout mouse. / Chua, Anita; Drake, S.F.; Herbison, C.E.; Olynyk, John; Leedman, Peter; Trinder, Debbie.

    In: Journal of Hepatology, Vol. 44, No. 1, 2006, p. 176-182.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Limited iron export by hepatocytes contributes to hepatic iron-loading in the Hfe knockout mouse

    AU - Chua, Anita

    AU - Drake, S.F.

    AU - Herbison, C.E.

    AU - Olynyk, John

    AU - Leedman, Peter

    AU - Trinder, Debbie

    PY - 2006

    Y1 - 2006

    N2 - Background/Aims: In hereditary hemochromatosis, iron-loading of hepatocytes is associated with increased iron uptake while little is known about iron release. This study aims to characterise iron release and ferroportin expression by Hfe knockout hepatocytes to determine if they contribute to iron overload in haemochromatosis.Methods: Iron release by hepatocytes from Hfe knockout, non-iron-loaded and iron-loaded wild-type mice was measured after incubation with nontransferrin-bound iron as iron-citrate.Results: Iron release and ferroportin expression by hepatocytes from Hfe knockout, non-iron-loaded and in vivo iron-loaded wild-type mice were similar although, nontransferrin-bound iron uptake was significantly increased in Hfe knockout hepatocytes and decreased in iron-loaded wild-type hepatocytes compared with non-iron-loaded wild-type cells. When expressed as a percentage of total iron uptake, iron release was decreased in Hfe knockout hepatocytes (4.6 +/- 0.7 versus 13.7 +/- 1.2%, P < 0.0001) and increased in iron-loaded wild-type hepatocytes (29.5 +/- 0.5 versus 13.5 +/- 0.7%; P < 0.0001) compared with wild-type hepatocytes. In contrast, in vitro iron-loading increased iron release and ferroportin expression by both Hfe knockout and wild-type hepatocytes.Conclusions: Hfe knockout hepatocytes accumulate iron as a result of limited iron export and enhanced iron uptake. The correlation between iron release and ferroportin expression suggests that iron export in hepatocytes is mediated by ferroportin. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

    AB - Background/Aims: In hereditary hemochromatosis, iron-loading of hepatocytes is associated with increased iron uptake while little is known about iron release. This study aims to characterise iron release and ferroportin expression by Hfe knockout hepatocytes to determine if they contribute to iron overload in haemochromatosis.Methods: Iron release by hepatocytes from Hfe knockout, non-iron-loaded and iron-loaded wild-type mice was measured after incubation with nontransferrin-bound iron as iron-citrate.Results: Iron release and ferroportin expression by hepatocytes from Hfe knockout, non-iron-loaded and in vivo iron-loaded wild-type mice were similar although, nontransferrin-bound iron uptake was significantly increased in Hfe knockout hepatocytes and decreased in iron-loaded wild-type hepatocytes compared with non-iron-loaded wild-type cells. When expressed as a percentage of total iron uptake, iron release was decreased in Hfe knockout hepatocytes (4.6 +/- 0.7 versus 13.7 +/- 1.2%, P < 0.0001) and increased in iron-loaded wild-type hepatocytes (29.5 +/- 0.5 versus 13.5 +/- 0.7%; P < 0.0001) compared with wild-type hepatocytes. In contrast, in vitro iron-loading increased iron release and ferroportin expression by both Hfe knockout and wild-type hepatocytes.Conclusions: Hfe knockout hepatocytes accumulate iron as a result of limited iron export and enhanced iron uptake. The correlation between iron release and ferroportin expression suggests that iron export in hepatocytes is mediated by ferroportin. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

    U2 - 10.1016/j.jhep.2005.08.012

    DO - 10.1016/j.jhep.2005.08.012

    M3 - Article

    VL - 44

    SP - 176

    EP - 182

    JO - Journal of Hepatology

    JF - Journal of Hepatology

    SN - 0168-8278

    IS - 1

    ER -