Artemisitene activates the Nrf2-dependent antioxidant response and protects against bleomycin-induced lung injury

Weimin Chen, Shanshan Li, Jinwei Li, Wen Zhou, Shouhai Wu, Shengmei Xu, Ke Cui, Donna Zhang, Bo Liu

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial regulator of the cellular antioxidant response and xenobiotic metabolism. Activation of the Nrf2 signaling pathway has been demonstrated to confer protection against environmental insults and prevent disease or inhibit the progression of diseases related to oxidative stress. In an attempt to identify novel improved Nrf2 inducers for systemic protection against tissue damage by environmental insults, we identified artemisitene as a novel Nrf2 activ ator using antioxidant responsive element luciferase assay in MDA-MB-231 cells. Further studies suggest that artemisitene activates Nrf2 by decreasing Nrf2 ubiquitination and increasing its stability. In Nrf2 wild-type mice, systemic administration of artemisitene strongly inhibits bleomycininduced lung damage. Artemisitene represents a novel class of Nrf2 inducer, and artemisitene-based therapeutic approach targeting Nrf2 may also provide antioxidant protection for humans against tissue damage by toxic chemicals.-Chen, W., Li, S., Li, J., Zhou, W., Wu, S., Xu, S.,Cui, K., Zhang, D.D.,Liu,B.ArtemisiteneactivatestheNrf2-dependent antioxidant response and protects against bleomycin-induced lung injury.

Original languageEnglish (US)
Pages (from-to)2500-2510
Number of pages11
JournalFASEB Journal
Volume30
Issue number7
DOIs
Publication statusPublished - Jul 1 2016

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Keywords

  • Keap1-nrf2 pathway
  • Nrf2 activator activator
  • Oxidative damage

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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