Cadmium depletes cellular iron availability through enhancing ferroportin translation via iron responsive element

Sun,Li; Wang,Lixin; Wang,Zhe; He,Wei; Zhang,Shuping; Guo,Wenli; Qian,Yi; Ji,Hong; Rong,Haiqin; Liu,Sijin

doi:10.3892/mmr.2014.3015

Cadmium depletes cellular iron availability through enhancing ferroportin translation via iron responsive element

Authors:
- Li Sun
- Lixin Wang
- Zhe Wang
- Wei He
- Shuping Zhang
- Wenli Guo
- Yi Qian
- Hong Ji
- Haiqin Rong
- Sijin Liu
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Affiliations: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco‑Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, P.R. China, Shandong Institute of Endocrine and Metabolic Diseases, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China
Published online on: November 27, 2014 https://doi.org/10.3892/mmr.2014.3015
Pages: 3129-3133

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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.

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