SHP-2 phosphatase controls aryl hydrocarbon receptor-mediated ER stress response in mast cells

Hsueh Chun Wang, Yufeng Zhou, Shau Ku Huang

研究成果: 雜誌貢獻文章同行評審

10 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)1739-1748
頁數10
期刊Archives of Toxicology
91
發行號4
DOIs
出版狀態已發佈 - 四月 1 2017
對外發佈Yes

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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