Iron loading and erythrophagocytosis increase ferroportin 1 (FPN1) expression in J774 macrophages
Open accessAbstract
The expression of ferroportin1 (FPN1) in reticuloendothelial macrophages supports the hypothesis that this iron-export protein participates in iron recycling from senescent erythrocytes. To gain insight into FPN1's role in macrophage iron metabolism, we examined the effect of iron status and erythrophagocytosis on FPN1 expression in J774 macrophages. Northern analysis indicated that FPN1 mRNA levels decreased with iron depletion and increased on iron loading. The iron-induced induction of FPN1 mRNA was blocked by actinomycin D, suggesting that transcriptional control was responsible for this effect. After erythrophagocytosis, FPN1 mRNA levels were also up-regulated, increasing 8-fold after 4 hours and returning to basal levels by 16 hours. Western analysis indicated corresponding increases in FPN1 protein levels, with maximal induction after 10 hours. Iron chelation suppressed FPN1 mRNA and protein induction after erythrophagocytosis, suggesting that FPN1 induction results from erythrocyte-derived iron. Comparative Northern analyses of iron-related genes after erythrophagocytosis revealed a 16-fold increase in FPN1 levels after 3 hours, a 10-fold increase in heme oxygenase-1 (HO-1) after 3 hours, a 2-fold increase in natural resistance macrophage-associated protein 1 (Nramp1) levels after 6 hours, but no change in divalent metal ion transporter 1 (DMT1) levels. The rapid and strong induction of FPN1 expression after erythrophagocytosis suggests that FPN1 plays a role in iron recycling. (Blood. 2003;102:4191-4197)
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Both yeast and human frataxin are processed to a mature form in two sequential cleavage steps with a mitochondrial processing peptidase (MPP).
“It was shown that both yeast and human frataxin are processed to a mature form in two sequential cleavage steps with a mitochondrial processing peptidase (MPP) (28, 43, 167)”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [167]
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References 57 · Cited by 227
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- Authors
- Knutson, M. D., Vafa, M. R., Haile, D. J., & Wessling-Resnick, M.
- Affiliations
- Harvard University (US)
- From the Department of Nutrition, Harvard School of Public Health, Boston, MA; Department of Social Medicine, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Medicine, University of Texas Health Science Center, San Antonio; and the Audie Murphy Veterans Affairs Hospital, South Texas Veterans Health System, San Antonio.
- ORCID
- Knutson, Mitchell D.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2003-12-01
- Volume
- 102
- Issue
- 12
- Pages
- 4191-4197
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1979621257
- Cited by
- 227
- References
- 57
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 4 · 2022: 10 · 2021: 7 · 2020: 15 · 2019: 5 · 2018: 8 · 2017: 8 · 2016: 7 · 2015: 4 · 2014: 14 · 2013: 10 · 2012: 14
- FWCI
- 5.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1f32dk009998-01a1)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK056160, DK09998, DK59429, DK56160, R01DK059429)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- ferroportin 1, erythrophagocytosis, iron recycling, macrophages, J774 macrophages, iron loading, iron depletion, heme oxygenase-1, NRAMP1, transcriptional regulation, reticuloendothelial cells, senescent erythrocytes
- MeSH terms
- Ferroportin, Animals, Cell Line, Erythrocytes, Ferritins, Gene Expression Regulation, Hemolysis, Humans, Iron, Kinetics, Macrophages, Phagocytosis, RNA, Messenger, Transcription, Genetic, Cation Transport Proteins, Mice, Rats
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