title: High levels of Mn²⁺ inhibit secretory pathway Ca²⁺/Mn²⁺-ATPase (SPCA) activity and cause Golgi fragmentation in neurons and glia.
abstract: 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 this 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 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 cocultures 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.
authors: Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, Badajoz, Spain.
authors: M Rosario
authors: MR
authors: Sepúlveda
authors: Frank
authors: F
authors: Wuytack
authors: Ana M
authors: AM
authors: Mata
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006056:Golgi Apparatus / Q000473:pathology*; D007150:Immunohistochemistry; D008345:Manganese / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D009498:Neurotoxins / Q000633:toxicity; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055571:Secretory Pathway / Q000187:drug effects
chemical_list: D009498:Neurotoxins; D008345:Manganese; C492024:Atp2c1 protein, mouse; D000252:Calcium-Transporting ATPases