p73 gene in dopaminergic neurons is highly susceptible to manganese neurotoxicity

Kim, Dong-Suk, Jin, Huajun, Anantharam, Vellareddy, Gordon, Richard, Kanthasamy, Arthi and Kanthasamy, Anumantha G. (2016) p73 gene in dopaminergic neurons is highly susceptible to manganese neurotoxicity. NeuroToxicology, . doi:10.1016/j.neuro.2016.04.012


Author Kim, Dong-Suk
Jin, Huajun
Anantharam, Vellareddy
Gordon, Richard
Kanthasamy, Arthi
Kanthasamy, Anumantha G.
Title p73 gene in dopaminergic neurons is highly susceptible to manganese neurotoxicity
Journal name NeuroToxicology   Check publisher's open access policy
ISSN 1872-9711
0161-813X
Publication date 2016-04-20
Sub-type Article (original research)
DOI 10.1016/j.neuro.2016.04.012
Open Access Status Not Open Access
Total pages 9
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Subject 2800 Neuroscience
3005 Toxicology
Formatted abstract
Chronic exposure to elevated levels of manganese (Mn) has been linked to a Parkinsonian-like movement disorder, resulting from dysfunction of the extrapyramidal motor system within the basal ganglia. However, the exact cellular and molecular mechanisms of Mn-induced neurotoxicity remain elusive. In this study, we treated C57BL/6J mice with 30. mg/kg Mn via oral gavage for 30 days. Interestingly, in nigral tissues of Mn-exposed mice, we found a significant downregulation of the truncated isoform of p73 protein at the N-terminus (δNp73). To further determine the functional role of Mn-induced p73 downregulation in Mn neurotoxicity, we examined the interrelationship between the effect of Mn on p73 gene expression and apoptotic cell death in an N27 dopaminergic neuronal model. Consistent with our animal study, 300. μM Mn treatment significantly suppressed p73 mRNA expression in N27 dopaminergic cells. We further determined that protein levels of the δNp73 isoform was also reduced in Mn-treated N27 cells and primary striatal cultures. Furthermore, overexpression of δNp73 conferred modest cellular protection against Mn-induced neurotoxicity. Taken together, our results demonstrate that Mn exposure downregulates p73 gene expression resulting in enhanced susceptibility to apoptotic cell death. Thus, further characterization of the cellular mechanism underlying p73 gene downregulation will improve our understanding of the molecular underpinnings of Mn neurotoxicity.
Keyword Manganese
Neurotoxicity
P73
δNp73
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Biomedical Sciences Publications
 
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Created: Fri, 27 May 2016, 20:54:36 EST by Richard Gordon on behalf of Learning and Research Services (UQ Library)