TY - JOUR
T1 - Artemisitene activates the Nrf2-dependent antioxidant response and protects against bleomycin-induced lung injury
AU - Chen, Weimin
AU - Li, Shanshan
AU - Li, Jinwei
AU - Zhou, Wen
AU - Wu, Shouhai
AU - Xu, Shengmei
AU - Cui, Ke
AU - Zhang, Donna D.
AU - Liu, Bo
N1 - Funding Information:
This study is supported by the National Natural Science Foundation of China (Nos. 81473294 and 81202398), and a grant from Chinese Ministry of Science and Technology (2013CB966902). The authors declare no conflicts of interest.
Publisher Copyright:
© FASEB.
PY - 2016/7
Y1 - 2016/7
N2 - 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.
AB - 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.
KW - Keap1-nrf2 pathway
KW - Nrf2 activator activator
KW - Oxidative damage
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U2 - 10.1096/fj.201500109R
DO - 10.1096/fj.201500109R
M3 - Article
C2 - 27006451
AN - SCOPUS:84978043675
VL - 30
SP - 2500
EP - 2510
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 7
ER -