| High levels of Mn(2+) inhibit secretory pathway Ca(2+) /Mn(2+) -ATPase (SPCA) activity and cause Golgi fragmentation in neurons and glia. | |
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MedLine Citation:
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PMID: 22845487 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Excess Mn(2+) in humans causes a neurological disorder known as manganism, which shares symptoms with Parkinson's disease. However, the cellular mechanisms underlying Mn(2+) -neurotoxicity and the involvement of Mn(2+) -transporters in cellular homeostasis and repair are poorly understood and require further investigation. In the current work, we have analyzed the effect of Mn(2+) on neurons and glia from mice in primary cultures. Mn(2+) overload compromised survival of both cell types, specifically affecting cellular integrity and Golgi organization, where the Secretory Pathway Ca(2+) /Mn(2+) -ATPase (SPCA1) is localized. This ATP-driven Mn(2+) transporter might take part in Mn(2+) accumulation/detoxification at low loads of Mn(2+) , but its ATPase activity is inhibited at high concentration of Mn(2+) . Glial cells appear to be significantly more resistant to this toxicity than neurons and their presence in co-cultures provided some protection to neurons against degeneration induced by Mn(2+) . Interestingly, the Mn(2+) toxicity was partially reversed upon Mn(2+) removal by wash out or by the addition of EDTA as a chelating agent, in particular in glial cells. These studies provide data on Mn(2+) neurotoxicity and may contribute to explore new therapeutic approaches for reducing Mn(2+) poisoning. © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry. |
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Authors:
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M Rosario Sepúlveda; Frank Wuytack; Ana M Mata |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-7-27 |
Journal Detail:
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Title: Journal of neurochemistry Volume: - ISSN: 1471-4159 ISO Abbreviation: - Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-7-31 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry. |
Affiliation:
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Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, 06006 Badajoz, Spain. Laboratory of Cellular Transport Systems, Department of Molecular Cell Biology, Faculty of Medicine, Katholieke Universiteit Leuven, 3000 Leuven, Belgium. |
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