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Downregulation of Mfn2 participates in manganese-induced neuronal apoptosis in rat striatum and PC12 cells.

Authors: Liu, Xinhang  Yang, Jianbin  Lu, Chunhua  Jiang, Shengyang  Nie, Xiaoke  Han, Jingling  Yin, Lifeng  Jiang, Junkang 
Citation: Liu X, etal., Neurochem Int. 2017 Feb 21. pii: S0197-0186(16)30405-3. doi: 10.1016/j.neuint.2017.02.008.
Pubmed: (View Article at PubMed) PMID:28232070
DOI: Full-text: DOI:10.1016/j.neuint.2017.02.008

Manganese (Mn) is a widely distributed trace element that is essential for normal brain function and development. However, chronic exposure to excessive Mn has been known to lead to neuronal loss and manganism, a disease with debilitating motor and cognitive deficits, whose clinical syndrome resembling idiopathic Parkinson's disease (IPD). However, the precise molecular mechanism underlying Mn neurotoxicity remains largely unclear. Accumulating evidence indicates that abnormal mitochondrial functionality is an early and causal event in Mn-induced neurodegeneration and apoptosis. Here, we investigated whether Mitofusin 2 (Mfn2), a highly conserved dynamin-related protein (DRP), played a role in the regulation of Mn-induced neuronal apoptosis. We revealed that Mfn2 was significantly dysregulated in rat striatum and PC12 neuronal-like cells following Mn exposure. Western blot analysis revealed that the expression of Mfn2 was remarkably decreased following different concentrations of Mn exposure. Immunohistochemistry analysis confirmed a remarkable downregulation of Mfn2 in rat striatum after Mn exposure. Immunofluorescent staining showed that Mfn2 was expressed predominantly in neurons, and neuronal loss of Mfn2 was associated with the expression of active caspase-3 following Mn exposure. Importantly, overexpression of Mfn2 apparently attenuated Mn-induced neuronal apoptosis. Notably, treatment with caspase-3 inhibitor Ac-DEVD-CH could not rescue Mn-induced downregulation of Mfn2, suggesting that Mn-induced mfn2 occurs prior to neuronal apoptosis. Taken together, these results indicated that down-regulated expression of Mfn2 might contribute to the pathological processes underlying Mn neurotoxicity.


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CRRD Object Information
CRRD ID: 12910738
Created: 2017-06-22
Species: All species
Last Modified: 2017-06-22
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.