High levels of Mn2+ inhibit secretory pathway Ca2+/Mn2+-ATPase (SPCA) activity and cause Golgi fragmentation in neurons and glia

Authors

  • M. Rosario Sepúlveda,

    1. Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, Badajoz, Spain
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  • Frank Wuytack,

    1. Laboratory of Cellular Transport Systems, Department of Molecular Cell Biology, Faculty of Medicine, Katholieke Universiteit Leuven, Leuven, Belgium
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  • Ana M. Mata

    Corresponding author
    • Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, Badajoz, Spain
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Address correspondence and reprint requests to Ana M. Mata, Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, 06006 Badajoz, Spain. E-mail: anam@unex.es

Abstract

Excess Mn2+ in humans causes a neurological disorder known as manganism, which shares symptoms with Parkinson's disease. However, the cellular mechanisms underlying Mn2+-neurotoxicity and the involvement of Mn2+-transporters in cellular homeostasis and repair are poorly understood and require further investigation. In this work, we have analyzed the effect of Mn2+ on neurons and glia from mice in primary cultures. Mn2+ overload compromised survival of both cell types, specifically affecting cellular integrity and Golgi organization, where the secretory pathway Ca2+/Mn2+-ATPase is localized. This ATP-driven Mn2+ transporter might take part in Mn2+ accumulation/detoxification at low loads of Mn2+, but its ATPase activity is inhibited at high concentration of Mn2+. Glial cells appear to be significantly more resistant to this toxicity than neurons and their presence in cocultures provided some protection to neurons against degeneration induced by Mn2+. Interestingly, the Mn2+ toxicity was partially reversed upon Mn2+ removal by wash out or by the addition of EDTA as a chelating agent, in particular in glial cells. These studies provide data on Mn2+ neurotoxicity and may contribute to explore new therapeutic approaches for reducing Mn2+ poisoning.

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