期刊
GENE
卷 532, 期 1, 页码 146-151出版社
ELSEVIER
DOI: 10.1016/j.gene.2013.09.023
关键词
PCB-77; Hepatocytes; Hepcidin; Iron homeostasis
资金
- Chinese Academy of Sciences [KZCX2-EW-404]
- National Natural Science Foundation of China [21077128, 20921063, 21177151, 21207152]
- Chinese Academy of Sciences program Hundreds Talents
PCBs are a family of persistent environmental toxicants with a wide spectrum of toxic features, such as immunotoxicity, hepatoxicity, endocrine disruption effects, and oncogenic effects. To date, little has been done to investigate the potential influence of PCB exposure on iron metabolism. Deregulated iron would lead to either iron deficiency or iron excess, coupled with various diseases such as anemia or hemochromatosis. Iron metabolism is strictly governed by the hepcidin-ferroportin axis, and hepcidin is the key regulator that is secreted by hepatocytes. Here, we found that PCB-77 could go through plasma membrane and accumulate in hepatocytes. PCB-77 was demonstrated to suppress hepcidin expression in HepG2 and L-02 hepatocytes. Moreover, hepatic hepcidin was observed to be inhibited in mice upon administration of PCB-77. Due to reduced hepcidin concentration, serum iron content was increased, with a significant reduction of splenic iron content Together, we deciphered the molecular mechanism responsible for PCB-conducted disturbance on iron homeostasis, i.e. through misregulating hepatic hepcidin expression. (C) 2013 Elsevier B.V. All rights reserved.
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