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High levels of Mn(2+) inhibit secretory pathway Ca(2+) /Mn(2+) -ATPase (SPCA) activity and cause Golgi fragmentation in neurons and glia.
MedLine Citation:
PMID:  22845487     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
M Rosario Sepúlveda; Frank Wuytack; Ana M Mata
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-27
Journal Detail:
Title:  Journal of neurochemistry     Volume:  -     ISSN:  1471-4159     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.
Affiliation:
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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