Abstract：
:Previously we reported that exposure of mouse and human mast cells to aryl hydrocarbon receptor (AhR) ligands resulted in reactive oxygen species (ROS)- and calcium (Ca2+)-dependent activation of mast cells in vitro and in vivo. However, the mechanisms through which the AhR-ligand axis mediates stress response, Ca2+ signaling and subsequent mast cell activation remain to be fully elucidated. Evidence is provided herein that SHP-2 is critical in regulating AhR-mediated ER stress response and intracellular Ca2+ dynamics. We found that an AhR ligand, FICZ, induced significant reduction of intracellular GSH and an increased level of intracellular ROS. Significantly, we showed that in FICZ-treated mast cells, SHP-2 promoted, in a ROS-dependent manner, ER stress response involving primarily the PERK signaling pathway, ATF4 activation and eIF2α phosphorylation, which could be reversed by the addition of an antioxidant, NAC, and was inhibited in cells with SHP-2 knockdown. Our findings suggested that SHP-2 is critical in controlling ER stress signals in response to AhR activation, which provides a new mechanistic insight into how the AhR-ligand axis regulates cellular adaptation to the environmental insult in mast cells.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Wang HC,Zhou Y,Huang SKdoi
10.1007/s00204-016-1861-1subject
Has Abstractpub_date
2017-04-01 00:00:00pages
1739-1748issue
4eissn
0340-5761issn
1432-0738pii
10.1007/s00204-016-1861-1journal_volume
91pub_type
杂志文章abstract：:The efficacy of oxime (HI-6, toxogonin or PAM Cl) therapy against GF (cyclohexyl methylphosphonofluoridate) poisoning was assessed in mice. It was found that the combinations of atropine and either toxogonin or HI-6 were effective therapies against GF poisoning. PAM therapy was ineffective. HI-6 was the only oxime whi...
journal_title：Archives of toxicology
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更新日期：2016-08-01 00:00:00
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journal_title：Archives of toxicology
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doi：10.1007/BF01974070
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pub_type： 杂志文章
doi：10.1007/s002040050243
更新日期：1995-01-01 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-008-0302-1
更新日期：2008-11-01 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-015-1490-0
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journal_title：Archives of toxicology
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更新日期：1983-10-01 00:00:00
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更新日期：2009-06-01 00:00:00
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journal_title：Archives of toxicology
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journal_title：Archives of toxicology
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更新日期：2020-10-17 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章,评审
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更新日期：2017-02-01 00:00:00
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journal_title：Archives of toxicology
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journal_title：Archives of toxicology
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更新日期：1979-10-01 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章
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更新日期：2020-02-01 00:00:00
abstract：:The deleterious effect of lead has been attributed to lead-induced oxidative stress with the consequence of lipid peroxidation. The present study was designed to investigate the combined effect of DL-alpha-lipoic acid (LA) and meso-2,3-dimercaptosuccinic acid (DMSA) on lead-induced peroxidative damages in rat kidney. ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-002-0350-x
更新日期：2002-08-01 00:00:00
