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Differential regulation of estrogen in iron metabolism in astrocytes and neurons
Author(s) -
Xu Manman,
Tan Xu,
Li Na,
Wu Hao,
Wang Yue,
Xie Junxia,
Wang Jun
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27188
Subject(s) - dmt1 , estrogen , downregulation and upregulation , metabolism , astrocyte , endocrinology , medicine , chemistry , ferroportin , transporter , biology , microbiology and biotechnology , biochemistry , central nervous system , gene , iron homeostasis
Previous studies have demonstrated an effect of estrogen on iron metabolism in peripheral tissues. The role of estrogen on brain iron metabolism is currently unknown. In this study, we investigated the effect and mechanism of estrogen on iron transport proteins. We demonstrated that the iron exporter ferroportin 1 (FPN1) and iron importer divalent metal transporter 1 (DMT1) were upregulated and iron content was decreased after estrogen treatment for 12 hr in primary cultured astrocytes. Hypoxia‐inducible factor‐1 alpha (HIF‐1α) was upregulated, but HIF‐2α remained unchanged after estrogen treatment for 12 hr in primary cultured astrocytes. In primary cultured neurons, DMT1 was downregulated, FPN1 was upregulated, iron content decreased, iron regulatory protein (IRP1) was downregulated, but HIF‐1α and HIF‐2α remained unchanged after estrogen treatment for 12 hr. These results suggest that the regulation of iron metabolism by estrogen in astrocytes and neurons is different. Estrogen increases FPN1 and DMT1 expression by inducing HIF‐1α in astrocytes, whereas decreased expression of IRP1 may account for the decreased DMT1 and increased FPN1 expression in neurons.