Lead-induced iron overload and attenuated effects of ferroportin 1 overexpression in PC12 cells

被引:18
作者
Zhou, Fankun [1 ,2 ]
Chen, Ying [2 ]
Fan, Guangqin [1 ,2 ]
Feng, Chang [2 ]
Du, Guihua [2 ]
Zhu, Gaochun [3 ]
Li, Yanshu [2 ]
Jiao, Huan [2 ]
Guan, Linfu [2 ]
Wang, Zhiping [2 ]
机构
[1] Nanchang Univ, State Key Lab Food Sci & Technol, Nanchang 330047, Peoples R China
[2] Nanchang Univ, Sch Publ Hlth, Dept Occupat Hlth & Toxicol, Nanchang 330006, Peoples R China
[3] Nanchang Univ, Sch Med, Dept Anat, Nanchang 330006, Peoples R China
关键词
Lead; Iron; Ferroportin; 1; Overexpression; PC12; cells; Neurotoxicity; METAL-ION TRANSPORTER-1; MESSENGER-RNA ISOFORMS; ALZHEIMERS-DISEASE; INFANTILE EXPOSURE; OXIDE NANOPARTICLES; RESPONSIVE ELEMENT; OXIDATIVE STRESS; TEA CATECHINS; EXPRESSION; HEPCIDIN;
D O I
10.1016/j.tiv.2014.07.005
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Lead (Pb) neurotoxicity has received renewed interest with the growing evidence that Pb contributes to Alzheimer's disease (AD). However, the mechanism is not clear. In our previous study of long-term Pb exposure in vivo, a brain iron (Fe) overload induced by Pb was observed in elderly rats. It is well known that brain Fe overload is the mechanism of AD. Therefore, we have reason to believe that Pb induced Fe overload and caused neurodegenerative disease. However, the mechanism or route of Pb-induced Fe overload is unknown. In the current study, the effect of Pb exposure on Fe homeostasis in PC12 cells was determined at different Pb-exposure concentrations and periods with differing Fe exposure, and the role of ferroportin 1 (FP1), the sole iron efflux protein, in Pb-induced Fe metabolic disorders was further investigated. The results showed a Pb-induced cellular increase in Fe accompanying a decrease in the expression of FP1 in a concentration-and time-dependent manner in Pb-exposed PC12 cells. Furthermore, FP1 overexpression could attenuate Fe accumulation in Pb-exposed PC12 cells. These results indicated that FP1 might be a novel target to prevent cellular Fe accumulation induced by Pb exposure and subsequent neurotoxic consequences. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1339 / 1348
页数:10
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