These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: P53-dependent induction of ferroptosis is required for artemether to alleviate carbon tetrachloride-induced liver fibrosis and hepatic stellate cell activation.
    Author: Wang L, Zhang Z, Li M, Wang F, Jia Y, Zhang F, Shao J, Chen A, Zheng S.
    Journal: IUBMB Life; 2019 Jan; 71(1):45-56. PubMed ID: 30321484.
    Abstract:
    Ferroptosis is recently reported as a new mode of regulated cell death. Its essential characteristics are disturbed redox homeostasis, overloaded iron, and increased lipid peroxidation. However, the role of ferroptosis in liver fibrosis remains poorly understood. In this study, we attempted to investigate the effect of artemether (ART) on ferroptosis in hepatic fibrosis and to further clarify the possible mechanisms. Our data showed that ART treatment markedly attenuated liver injury and reduced fibrotic scar formation in the mouse model of liver fibrosis. Moreover, experiments in vitro also confirmed that ART treatment significantly decreased expression of hepatic stellate cell (HSC) activation markers. Interestingly, HSCs treated by ART presented morphological features of ferroptosis. Furthermore, ART remarkably triggered ferroptosis by promoting the accumulation of iron and lipid peroxides, whereas inhibition of ferroptosis by specific inhibitor ferrostatin-1 (Fer-1) completely abolished ART-induced antifibrosis effect. More importantly, our discovery determined that tumor suppressor P53 was an upstream molecule in the facilitation of ART-induced HSC ferroptosis. Conversely, knockdown of P53 by siRNA evidently blocked ART-induced HSC ferroptosis in turn exacerbated liver fibrosis. Overall, our findings revealed that P53-dependent induction of ferroptosis is necessary for ART to ameliorate CCl4 -induced hepatic fibrosis and inhibit HSC activation. © 2018 IUBMB Life, 71(1):45-56, 2019.
    [Abstract] [Full Text] [Related] [New Search]