PCB-77 disturbs iron homeostasis through regulating hepcidin gene expression

Wang, L; Zhang, S; Lin, R; Li, L; Zhang, D; Li, X; Liu, S

HERO ID

2149558

Reference Type

Journal Article

Year

2013

Language

English

PMID

24055725

HERO ID 2149558
In Press No
Year 2013
Title PCB-77 disturbs iron homeostasis through regulating hepcidin gene expression
Authors Wang, L; Zhang, S; Lin, R; Li, L; Zhang, D; Li, X; Liu, S
Journal Gene
Volume 532
Issue 1
Page Numbers 146-151
Abstract 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.
Doi 10.1016/j.gene.2013.09.023
Pmid 24055725
Wosid WOS:000326554300021
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English
Keyword PCB-77; Hepatocytes; Hepcidin; Iron homeostasis