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PMID: 14973193 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Copper-induced ferroportin-1 expression in J774 macrophages is associated with increased iron efflux.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 9 ·2004-03-02 ·Pages 2700-5

Chung J, Haile DJ, Wessling-Resnick M

Abstract

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 microM CuSO(4) for up to 20 h. Copper treatment significantly increased FPN1 mRNA in a dose- and time-dependent manner. After 20 h, 100 microM CuSO(4) up-regulated FPN1 transcript levels approximately 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 in (59)Fe 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.

MeSH Terms
Animals Cation Transport Proteins/genetics Cell Line Copper/pharmacology Gene Expression Regulation/drug effects Iron/metabolism Mice Phagocytosis/drug effects RNA, Messenger/genetics
Chemicals
Cation Transport Proteins RNA, Messenger metal transporting protein 1 Copper Iron
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Chung Jayong
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Haile David J
Wessling-Resnick Marianne
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0306622101
Published
2004-03-02
Epub
2004-00-18
Pages
2700-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC365684
Subset
IM
Grants
NIDDK NIH HHS · R01 DK056160 · United States
NIDDK NIH HHS · R01 DK059429 · United States
NIDDK NIH HHS · DK56160 · United States
NIDDK NIH HHS · DK59429 · United States
External Links
PubMed source DOI: 10.1073/pnas.0306622101 PMC Full Text View journal details
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