Abstract:
:Cadmium (Cd), is a well-known environmental and occupational hazard with a potent neurotoxic action. However, the mechanism underlying cadmium-induced neurotoxicity remains unclear. Herein, we exposed Neuro-2a cells to different concentrations of cadmium chloride (CdCl2) (12.5, 25 and 50 μM) for 24 h and found that Cd significantly induced lysosomal membrane permeabilization (LMP) with the release of cathepsin B (CTSB) to the cytosol, which in turn caused the release of mitochondrial cytochrome c (Cyt c) and eventually triggered caspase-dependent apoptosis. Interestingly, Cd decreased TFE3 expression but induced the nuclear translocation of TFE3 and TFE3 target-gene expression, which might be associated with lysosomal stress mediated by Cd. Notably, Tfe3 overexpression protected against Cd-induced neurotoxicity by maintaining the lysosomal-mitochondrial axis, and the protective effect of TFE3 is not dependent on the restoration of autophagic flux. In conclusion, our study demonstrated for the first time that lysosomal-mitochondrial axis dependent apoptosis, a neglected mechanism, may be the most important reason for Cd-induced neurotoxicity and that manipulation of TFE3 signaling may be a potential therapeutic approach for treatment of Cd-induced neurotoxicity.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Pi H,Li M,Xie J,Yang Z,Xi Y,Yu Z,Zhou Zdoi
10.1016/j.toxlet.2018.07.015subject
Has Abstractpub_date
2018-10-01 00:00:00pages
335-350eissn
0378-4274issn
1879-3169pii
S0378-4274(18)31502-9journal_volume
295pub_type
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doi:10.1016/j.toxlet.2014.09.013
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journal_title:Toxicology letters
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journal_title:Toxicology letters
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journal_title:Toxicology letters
pub_type: 杂志文章,评审
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journal_title:Toxicology letters
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journal_title:Toxicology letters
pub_type: 杂志文章
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更新日期:2005-01-15 00:00:00
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journal_title:Toxicology letters
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journal_title:Toxicology letters
pub_type: 杂志文章
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更新日期:2004-11-02 00:00:00
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journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2003.12.044
更新日期:2004-04-01 00:00:00