title: Cadmium depletes cellular iron availability through enhancing ferroportin translation via iron responsive element.
abstract: Cadmium (Cd) is a heavy metal that has detrimental effects on various organs. The widespread contamination of Cd in the environment, crops and food sources poses a severe threat to human health. Acute toxicities of Cd have been extensively investigated; however, the health impact of chronic low‑dose exposure to Cd, particularly exposure under non‑toxic concentrations, has yet to be elucidated. Furthermore, the toxic threshold of Cd is currently unknown. Ferroportin is the only known iron exporter in vertebrate cells, and it has an essential role in controlling iron egress from cells. To the best of our knowledge, the present study is the first to verify the regulation of ferroportin by Cd. Treatment with low‑dose Cd (i.e. at sublethal concentrations, without undermining cell viability) increased the protein expression of ferroportin in macrophages, and this was associated with depleted cellular iron levels. Mechanistic investigations revealed that Cd modulated the ferroportin concentration at the translational level, via the iron responsive element located at the 5'‑untranslated region of ferroportin. In conclusion, these data provide evidence for the molecular basis by which Cd alters cellular iron availability through elevating concentrations of ferroportin.
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco‑Environmental Sciences, Chinese Academy of Sciences, 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, Beijing 100085, P.R. China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco‑Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, P.R. China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco‑Environmental Sciences, Chinese Academy of Sciences, 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, 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, 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, Beijing 100085, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Qian
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, Beijing 100085, P.R. China.
authors.forename: Sijin
authors.initials: S
authors.lastname: Liu
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D002104:Cadmium / Q000494:pharmacology*; D019256:Cadmium Chloride / Q000494:pharmacology; D027682:Cation Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D007501:Iron / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D021381:Protein Transport; D020218:Response Elements; D000098742:Ferroportin
chemical_list: D020121:5' Untranslated Regions; D027682:Cation Transport Proteins; D000098742:Ferroportin; D002104:Cadmium; D007501:Iron; D019256:Cadmium Chloride