Copper-Induced Ferroportin-1 Expression in J774 Macrophages Is Associated with Increased Iron Efflux

Copper is known to play a role in iron recycling from macrophages. To examine whether cellular copper status affects expression of the iron exporter ferroportin-1 (FPN1), J774 macrophage cells were exposed to 10-100 μM CuSO4for up to 20 h. Copper treatment significantly increased FPN1 mRNA in a dose...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 101; no. 9; pp. 2700 - 2705
Main Authors Chung, Jayong, Haile, David J., Wessling-Resnick, Marianne, Law, John H.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 02.03.2004
National Acad Sciences
Subjects
Animals
Biological Sciences
Biology
Caco 2 cells
Cation Transport Proteins - genetics
Cell Line
Copper
Copper - pharmacology
Erythrocytes
Gene expression
Gene expression regulation
Gene Expression Regulation - drug effects
HeLa cells
Inductive reasoning
Iron
Iron - metabolism
Macrophages
Messenger RNA
Mice
Phagocytosis - drug effects
RNA
RNA, Messenger - genetics
Science
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Summary:Copper is known to play a role in iron recycling from macrophages. To examine whether cellular copper status affects expression of the iron exporter ferroportin-1 (FPN1), J774 macrophage cells were exposed to 10-100 μM CuSO4for up to 20 h. Copper treatment significantly increased FPN1 mRNA in a dose- and time-dependent manner. After 20 h, 100 μM CuSO4up-regulated FPN1 transcript levels ≈13-fold compared to untreated controls. Induction was detected 8 h after copper treatment was initiated and markedly increased thereafter. A corresponding increase in FPN1 protein levels was observed upon copper treatment. Induction of J774 cell FPN1 expression by copper was also associated with a dose-dependent increase in59Fe release after erythrophagocytosis of labeled red blood cells. Thus, a previously uncharacterized role for copper in the regulation of macrophage iron recycling is suggested by the induction of FPN1 gene expression and iron efflux by this metal.
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Edited by John H. Law, University of Arizona, Tucson, AZ
This paper was submitted directly (Track II) to the PNAS office.
To whom correspondence should be addressed. E-mail: wessling@hsph.harvard.edu.
Abbreviations: FPN1, ferroportin-1; TRIEN, triethylenetetramine; TfR, transferrin receptor; NTA, nitrilotriacetic acid; MRE, metal response elements.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0306622101