title: Sublethal exposure of organophosphate pesticide chlorpyrifos alters cellular iron metabolism in hepatocytes and macrophages.
abstract: Chlorpyrifos (CPF) is commonly used for agricultural and domestic applications, and its contamination is widely detected in environmental media, and in a broad spectrum of field crops, fruits and vegetables. CPF exposure causes many adverse effects on human health including hepatoxicity, neurotoxicity and endocrine disruption. However, few studies have been conducted thus far to investigate the potential influence of CPF exposure on iron metabolism at concentrations that do not trigger significant cell death. Iron metabolism is concertedly governed by the hepcidin-ferroportin axis, where hepcidin is the central hormone involved in the regulation of iron absorption and release, while ferroportin is the only known iron exporter that functions by iron egress from cells. In the present study, we demonstrated that CPF treatment at a non-toxic concentration greatly enhanced ferroportin gene transcription in human macrophage THP-1 cells. CPF significantly inhibited hepcidin expression in human hepatocyte HepG2 cells. As a result, the intracellular labile iron pool (LIP) was largely reduced in THP-1 and HepG2 cells. The combined data of this study identified a novel finding of CPF that disrupts iron homeostasis by altering ferroportin and hepcidin expression. These findings would be useful in understanding the biological effects of CPF exposure, especially under relatively low and non-toxic doses.
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Haidian, Beijing 100085, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Haidian, Beijing 100085, P.R. China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Haidian, Beijing 100085, P.R. China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Haidian, Beijing 100085, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Haidian, Beijing 100085, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Haidian, Beijing 100085, P.R. China.
authors.forename: Guangbo
authors.initials: G
authors.lastname: Qu
authors.affiliation: Shandong Institute of Endocrine and Metabolic Diseases, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.affiliation: Shandong Institute of Endocrine and Metabolic Diseases, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.
authors.forename: Haiqin
authors.initials: H
authors.lastname: Rong
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Haidian, Beijing 100085, P.R. China.
authors.forename: Sijin
authors.initials: S
authors.lastname: Liu
mesh_terms: D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004390:Chlorpyrifos / Q000633:toxicity*; D057809:HEK293 Cells; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D064451:Hepcidins / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D007501:Iron / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D000098742:Ferroportin
chemical_list: D027682:Cation Transport Proteins; D064451:Hepcidins; D007306:Insecticides; D000098742:Ferroportin; D007501:Iron; D004390:Chlorpyrifos