PCB-77 disturbs iron homeostasis through regulating hepcidin gene expression.
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.
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China.
Lei
L
Wang
Shuping
S
Zhang
Ronghai
R
Lin
Long
L
Li
Daoqiang
D
Zhang
Xinghong
X
Li
Sijin
S
Liu
D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects; D064451:Hepcidins / Q000235:genetics*; D006706:Homeostasis / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007501:Iron / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism
D064451:Hepcidins; D011078:Polychlorinated Biphenyls; D007501:Iron; C028451:3,4,3',4'-tetrachlorobiphenyl
3,3′,4,4′-tetrachlorobiphenyl; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; BMP; DMSO; ERE; GC–MS; Hepatocytes; Hepcidin; IL-6; Iron homeostasis; LDH; MTT; PCB-77; PCBs; bone morphogenetic protein; dimethylsulfoxide; estrogen response elements; gas chromatography–mass spectrometry; interleukin- 6; lactate dehydrogenase; polychlorinated biphenyls; qRT-PCR; quantitative real-time polymerase chain reaction