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Involvement of ADAM10 in acrolein-induced astrocytic inflamation
  • Date2021-02-23 16:08
  • Update2021-02-23 16:08
  • CountersignatureDivision of Research Planning
  • Tel043-719-8033

Toxicology Letters, 2020.318, 44-49, DOI: https://doi.org/10.1016/j.toxlet.2019.10.005


Involvement of ADAM10 in acrolein-induced astrocytic inflamation

Jung Hyun Park, Ji-Young Choi; Chulman Jo; Young Ho Koh


Abstract

    Acrolein is a neurotoxin produced through lipid peroxidation in the brain affected by ischemic stroke, which results in neuronal cell injury and inflammation. However the mechanism underlying acrolein-induced brain inflammation remains unclear. Therefore we examined how acrolein leads to astrocytic inflammation. It was found that acrolein increased the levels of NLRP3 and cleaved caspase-1, which led to the maturation of interleukin- 1β (IL-1β). ELISA assay results, which showed that acrolein increased the secreted IL-1β, further supported acrolein-induced astrocytic inflammation. Acrolein increased ADAM10 protein levels and the cleavage of N-cadherin. The ADAM10 inhibitor, GI 254023X blocked N-cadherin cleavage by acrolein, suggesting that ADAM10 is an upstream of N-cadherin. Furthermore, we found that acrolein activated p38 MAPK and NF-κB p65, while pretreatment with p38 MAPK inhibitor, SB203580 and GI 254023X inhibited NF-κB p65 activation and NLRP3 inflammasome. This suggests that p38 MAPK mediates the activation of NF-κB p65, which is associated with NLRP3 expression. Finally, we showed that acrolein induced cell toxicity and decrease of EAAT1 expression, suggesting that acrolein may induce a loss of glutamate uptake function. In conclusion, we demonstrate that acrolein induces astrocytic inflammation through NLRP3 inflammasome, which is regulated by ADAM10 and attributed to p38 MAPK-activated NF-κB p65 activity.



  • 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
  • This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.


This public work may be used under the terms of the public interest source This public work may be used under the terms of the public interest source
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