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Ceruloplasmin is Involved in the Nigral Iron Accumulation of 6-OHDA-Lesioned Rats

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Abstract

Elevated iron levels in the substantia nigra (SN) participate in neuronal death in Parkinson’s disease (PD), while the mechanisms underlying the increased iron are still unknown. Ceruloplasmin (CP), a ferroxidase, converts highly toxic ferrous iron to its non-toxic ferric form, which cooperated with ferroportin1 (FP1) facilitating the export of iron from cells. To elucidate if the abnormal expression of CP is involved in the nigral iron accumulation, here, we investigated CP expression in the SN of rats lesioned by 6-hydroxydopamine (6-OHDA). We showed that FP1 and CP colocalized in the rat SN. One day after 6-OHDA lesion, when there was a half reduction in the number of dopaminergic neurons, the iron level was increased compared with the normal rats; both the mRNA and protein expressions of CP decreased compared with the control. When rats began showing rotation behavior induced by apomorphine, usually after 6 weeks since 6-OHDA lesion, they are considered PD models. In these PD models, almost no dopaminergic neurons can be detected in the lesioned SN and nigral iron level was further increased. At this time point, a further decrease of CP was observed. These results show that FP1 and CP colocalize in the rat brain, indicating the coordinated actions of the two proteins in the cellular iron export, and suggest that decreased expression of CP in the SN is involved in the nigral iron accumulation of 6-OHDA-lesioned rats.

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Acknowledgments

This work was supported by grants from the National Program of Basic Research sponsored by the Ministry of Science and Technology of China (2011CB504102), and the National Foundation of Natural Science of China (31171031, 81430024).

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Authors and Affiliations

  1. Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao, 266071, China

    Jun Wang, Mingxia Bi & Junxia Xie

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  1. Jun Wang
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  2. Mingxia Bi
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Correspondence to Jun Wang or Junxia Xie.

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Wang, J., Bi, M. & Xie, J. Ceruloplasmin is Involved in the Nigral Iron Accumulation of 6-OHDA-Lesioned Rats. Cell Mol Neurobiol 35, 661–668 (2015). https://doi.org/10.1007/s10571-015-0161-2

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