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

Lead-induced iron overload and attenuated effects of ferroportin 1 overexpression in PC12 cells.
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DOI：
10.1016/j.tiv.2014.07.005
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发表时间：
2014-12
期刊：
Toxicology in vitro : an international journal published in association with BIBRA
影响因子：
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通讯作者：
Fankun Zhou;Ying Chen;Guangqin Fan;Chang Feng;Guihua Du;Gaochun Zhu;Yanshu Li;Huan Jiao;Linfu Gua
Fankun Zhou;Ying Chen;Guangqin Fan;Chang Feng;Guihua Du;Gaochun Zhu;Yanshu Li;Huan Jiao;Linfu Gua
中科院分区：
其他
文献类型：
--
作者：
Fankun Zhou;Ying Chen;Guangqin Fan;Chang Feng;Guihua Du;Gaochun Zhu;Yanshu Li;Huan Jiao;Linfu Gua

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随着越来越多的证据表明铅与阿尔茨海默病（AD）有关，铅的神经毒性引起了人们的新的关注。然而，其机制尚不清楚。在我们以前的长期铅暴露的研究中，在老年大鼠中观察到铅引起的脑铁（Fe）超载。众所周知，脑铁超载是AD的发病机制。因此，我们有理由相信，铅诱导铁超载，并导致神经退行性疾病。然而，铅诱导的铁过载的机制或途径是未知的。在本研究中，在不同的铅暴露浓度和时间与不同的铁暴露的影响，在PC 12细胞铁稳态的铅暴露，和ferroportin 1（FP1），唯一的铁外排蛋白，在铅诱导的铁代谢紊乱的作用进行了进一步研究。结果表明，铅诱导的细胞增加铁伴随着在铅暴露的PC12细胞中的浓度和时间依赖性的方式在FP1的表达下降。此外，FP1过表达可以减少铅暴露的PC12细胞中的铁积累。这些结果表明FP 1可能是一个新的靶点，可以防止铅暴露诱导的细胞铁积累和随后的神经毒性后果。
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.