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High levels of M n 2+ inhibit secretory pathway C a 2+ / M n 2+ ‐ ATP ase ( SPCA ) activity and cause Golgi fragmentation in neurons and glia
Author(s) -
Sepúlveda M. Rosario,
Wuytack Frank,
Mata Ana M.
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07888.x
Subject(s) - neurotoxicity , homeostasis , golgi apparatus , chemistry , microbiology and biotechnology , transporter , toxicity , biochemistry , biology , cell , gene , organic chemistry
Excess M n 2+ in humans causes a neurological disorder known as manganism, which shares symptoms with Parkinson's disease. However, the cellular mechanisms underlying M n 2+ ‐neurotoxicity and the involvement of M n 2+ ‐transporters in cellular homeostasis and repair are poorly understood and require further investigation. In this work, we have analyzed the effect of M n 2+ on neurons and glia from mice in primary cultures. M n 2+ overload compromised survival of both cell types, specifically affecting cellular integrity and Golgi organization, where the secretory pathway C a 2+ / M n 2+ ‐ ATP ase is localized. This ATP ‐driven M n 2+ transporter might take part in M n 2+ accumulation/detoxification at low loads of Mn 2+ , but its ATP ase activity is inhibited at high concentration of M n 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 M n 2+ . Interestingly, the M n 2+ toxicity was partially reversed upon M n 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 M n 2+ neurotoxicity and may contribute to explore new therapeutic approaches for reducing M n 2+ poisoning.