PMID- 34571908
OWN - NLM
STAT- MEDLINE
DCOM- 20211115
LR  - 20211115
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 10
IP  - 9
DP  - 2021 Aug 31
TI  - The Role of Copper in the Regulation of Ferroportin Expression in Macrophages.
LID - 10.3390/cells10092259 [doi]
LID - 2259
AB  - The critical function of ferroportin (Fpn) in maintaining iron homeostasis 
      requires complex and multilevel control of its expression. Besides iron-dependent 
      cellular and systemic control of Fpn expression, other metals also seem to be 
      involved in regulating the Fpn gene. Here, we found that copper loading 
      significantly enhanced Fpn transcription in an Nrf2-dependent manner in primary 
      bone-marrow-derived macrophages (BMDMs). However, prolonged copper loading 
      resulted in decreased Fpn protein abundance. Moreover, CuCl(2) treatment induced 
      Fpn expression in RAW 264.7 macrophages at both the mRNA and protein level. These 
      data suggest that cell-type-specific regulations have an impact on Fpn protein 
      stability after copper loading. Transcriptional suppression of Fpn after 
      lipopolysaccharide (LPS) treatment contributes to increased iron storage inside 
      macrophages and may result in anemia of inflammation. Here, we observed that in 
      both primary BMDMs and RAW 264.7 macrophages, LPS treatment significantly 
      decreased Fpn mRNA levels, but concomitant CuCl(2) stimulation counteracted the 
      transcriptional suppression of Fpn and restored its expression to the control 
      level. Overall, we show that copper loading significantly enhances Fpn 
      transcription in macrophages, while Fpn protein abundance in response to CuCl(2) 
      treatment, depending on macrophage type and factors specific to the macrophage 
      population, can influence Fpn regulation in response to copper loading.
FAU - Jonczy, Aneta
AU  - Jonczy A
AUID- ORCID: 0000-0002-4333-6853
AD  - Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, 
      Polish Academy of Sciences, 05-552 Jastrzebiec, Poland.
FAU - Mazgaj, Rafal
AU  - Mazgaj R
AUID- ORCID: 0000-0001-6706-0882
AD  - Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, 
      Polish Academy of Sciences, 05-552 Jastrzebiec, Poland.
FAU - Smuda, Ewa
AU  - Smuda E
AD  - Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, 
      Polish Academy of Sciences, 05-552 Jastrzebiec, Poland.
FAU - Zelazowska, Beata
AU  - Zelazowska B
AD  - Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, 
      Polish Academy of Sciences, 05-552 Jastrzebiec, Poland.
FAU - Kopec, Zuzanna
AU  - Kopec Z
AUID- ORCID: 0000-0001-5869-7670
AD  - Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, 
      Polish Academy of Sciences, 05-552 Jastrzebiec, Poland.
FAU - Starzynski, Rafal Radoslaw
AU  - Starzynski RR
AD  - Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, 
      Polish Academy of Sciences, 05-552 Jastrzebiec, Poland.
FAU - Lipinski, Pawel
AU  - Lipinski P
AD  - Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, 
      Polish Academy of Sciences, 05-552 Jastrzebiec, Poland.
LA  - eng
GR  - 2017/25/N/NZ3/01957/Narodowe Centrum Nauki/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210831
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Cation Transport Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (metal transporting protein 1)
RN  - 789U1901C5 (Copper)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Animals
MH  - Cation Transport Proteins/genetics/*metabolism
MH  - Copper/*pharmacology
MH  - Gene Expression Regulation/*drug effects
MH  - *Homeostasis
MH  - Iron/*metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/cytology/*drug effects/metabolism
MH  - Mice
PMC - PMC8469096
OTO - NOTNLM
OT  - LPS
OT  - Nrf2
OT  - copper
OT  - ferroportin
OT  - macrophages
COIS- The authors declare no conflict of interest.
EDAT- 2021/09/29 06:00
MHDA- 2021/11/16 06:00
PMCR- 2021/08/31
CRDT- 2021/09/28 01:04
PHST- 2021/08/02 00:00 [received]
PHST- 2021/08/22 00:00 [revised]
PHST- 2021/08/24 00:00 [accepted]
PHST- 2021/09/28 01:04 [entrez]
PHST- 2021/09/29 06:00 [pubmed]
PHST- 2021/11/16 06:00 [medline]
PHST- 2021/08/31 00:00 [pmc-release]
AID - cells10092259 [pii]
AID - cells-10-02259 [pii]
AID - 10.3390/cells10092259 [doi]
PST - epublish
SO  - Cells. 2021 Aug 31;10(9):2259. doi: 10.3390/cells10092259.