Journal
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
Volume 245, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2022.114083
Keywords
PM2; 5; System X c; Beclin1; Ferroptosis; Acute lung injury
Categories
Ask authors/readers for more resources
This study identified the role of ferroptosis in PM2.5-induced acute lung injury, revealing a novel mechanism involving the AMPK-Beclin1 pathway and System Xc-. The findings provide new insight into the toxicological effects of PM2.5 on respiratory problems.
Urban airborne fine particulate matter (PM2.5) is a global pollution source that has been strongly related to multiple respiratory diseases involving various types of regulated cell death (RCD). However, the role of ferroptosis, a novel form of RCD, in PM2.5-induced acute lung injury (ALI), has not been elucidated. Herein, we define the role and mechanism of ferroptosis in a PM2.5-induced ALI model. First, we demonstrated that lipid peroxidation and iron accumulation were significantly enhanced in ALI models and were accompanied by activation of the AMP-activated protein kinase (AMPK)-Beclin1 signaling pathway and inhibition of the key subunit SLC7A11 of System Xc-. However, these abnormalities were partially reversed by ferroptosis inhibitors. We further revealed that Beclin1 knockdown or overexpression ameliorated or exacerbated PM2.5-induced ferroptosis, respectively. Mechanistically, we verified that Beclin1 blocks System Xc- activity to trigger ferroptosis by directly binding to SLC7A11. Finally, knockdown of Beclin1 by AAV-shRNA or inhibition of AMPK, an upstream activator of Beclin1, ameliorated PM2.5-induced ferroptosis and ALI. Taken together, our results revealed that ferroptosis plays a novel role in PM2.5-induced ALI and elucidated the specific mechanism involving the AMPK-Beclin1 pathway and System Xc-, which may provide new insight into the toxicological effects of PM2.5 on respiratory problems.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available