PMID- 25660146
OWN - NLM
STAT- MEDLINE
DCOM- 20151215
LR  - 20150316
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Linking)
VI  - 27
IP  - 5
DP  - 2015 May
TI  - Estrogen contributes to regulating iron metabolism through governing ferroportin 
      signaling via an estrogen response element.
PG  - 934-42
LID - S0898-6568(15)00030-3 [pii]
LID - 10.1016/j.cellsig.2015.01.017 [doi]
AB  - Ferroportin (FPN) is the only known iron exporter in mammalian cells, and is 
      universally expressed in most types of cells. FPN signaling plays a crucial role 
      in maintaining iron homeostasis through governing the level of intracellular 
      iron. Serum iron storage is conversely related with the estrogen level in the 
      female bodies, and women in post-menopause are possibly subjected to iron 
      retention. However, the potential effects of estrogen on iron metabolism are not 
      clearly understood. Here, FPN mRNA transcription in all selected estrogen 
      receptor positive (ER+) cells was significantly reduced upon 17beta-estradiol (E2) 
      treatment; and this inhibitory effect could be attenuated by ER antagonist 
      tamoxifen. Likewise, in murine bone marrow-derived macrophages (BMDMs), FPN 
      reduction with elevated intracellular iron (reflected by increased ferritin) was 
      observed in response to E2; however, ferritin level barely responded to E2 in 
      FPN-null BMDMs. The observation of inhibition of FPN mRNA expression was not 
      replicated in ER(-) cells upon E2. A functional estrogen response element (ERE) 
      was identified within the promoter of FPN, and this ERE was responsible for the 
      suppressive effect of E2 on FPN expression. Moreover, ovariectomized (OVX) and 
      sham-operated (SHAM) mice were used to further confirm the in vitro finding. The 
      expression of hepatic FPN was induced in OVX mice, compared to that in the SHAM 
      mice. Taken together, our results demonstrated that estrogen is involved in 
      regulating FPN expression through a functional ERE on its promoter, providing 
      additional insights into a vital role of estrogen in iron metabolism.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Qian, Yi
AU  - Qian Y
AD  - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research 
      Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 
      100085, China; College of Biological and Environmental Engineering, Zhejiang 
      University of Technology, Hangzhou 310032, China.
FAU - Yin, Chunyang
AU  - Yin C
AD  - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research 
      Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 
      100085, China.
FAU - Chen, Yue
AU  - Chen Y
AD  - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research 
      Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 
      100085, China; Department of Urology, The Second Hospital of Tianjin Medical 
      University, Tianjin Institute of Urology, Tianjin 300211, China.
FAU - Zhang, Shuping
AU  - Zhang S
AD  - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research 
      Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 
      100085, China; Institute for Medical Engineering and Science, Massachusetts 
      Institute of Technology, Cambridge, MA 02139, USA.
FAU - Jiang, Li
AU  - Jiang L
AD  - Department of Nutrition, School of Public Health, Institute of Nutrition and Food 
      Safety, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious 
      Diseases, Zhejiang University, Hangzhou, Zhejiang 310027, China.
FAU - Wang, Fudi
AU  - Wang F
AD  - Department of Nutrition, School of Public Health, Institute of Nutrition and Food 
      Safety, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious 
      Diseases, Zhejiang University, Hangzhou, Zhejiang 310027, China.
FAU - Zhao, Meirong
AU  - Zhao M
AD  - College of Biological and Environmental Engineering, Zhejiang University of 
      Technology, Hangzhou 310032, China. Electronic address: zhaomr@zjut.edu.cn.
FAU - Liu, Sijin
AU  - Liu S
AD  - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research 
      Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 
      100085, China. Electronic address: sjliu@rcees.ac.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150204
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Cation Transport Proteins)
RN  - 0 (Estrogens)
RN  - 0 (RNA, Messenger)
RN  - 0 (metal transporting protein 1)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Animals
MH  - Cation Transport Proteins/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Estrogens/*metabolism
MH  - Female
MH  - Gene Expression Regulation
MH  - Humans
MH  - Iron/*metabolism
MH  - Mice, Inbred C57BL
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/genetics
MH  - Response Elements
MH  - *Signal Transduction
MH  - Transcription, Genetic
OTO - NOTNLM
OT  - Estrogen
OT  - Estrogen response element
OT  - Ferroportin
OT  - Iron
OT  - Ovariectomy
EDAT- 2015/02/11 06:00
MHDA- 2015/12/17 06:00
CRDT- 2015/02/10 06:00
PHST- 2015/01/15 00:00 [received]
PHST- 2015/01/31 00:00 [accepted]
PHST- 2015/02/10 06:00 [entrez]
PHST- 2015/02/11 06:00 [pubmed]
PHST- 2015/12/17 06:00 [medline]
AID - S0898-6568(15)00030-3 [pii]
AID - 10.1016/j.cellsig.2015.01.017 [doi]
PST - ppublish
SO  - Cell Signal. 2015 May;27(5):934-42. doi: 10.1016/j.cellsig.2015.01.017. Epub 2015 
      Feb 4.