PIEZO1 Ion Channel Mediates Ionizing Radiation-Induced Pulmonary Endothelial Cell Ferroptosis via Ca²⁺/Calpain/VE-Cadherin Signaling.

ABSTRACT: Pulmonary endothelial cell dysfunction plays an important role in ionizing radiation (IR)-induced lung injury. Whether pulmonary endothelial cell ferroptosis occurs after IR and what are the underlying mechanisms remain elusive. Here, we demonstrate that 15-Gy IR induced ferroptosis characterized by lethal accumulation of reactive oxygen species (ROS), lipid peroxidation, mitochondria shrinkage, and decreased glutathione peroxidase 4 (GPX4) and SLC7A11 expression in pulmonary endothelial cells. The phenomena could be mimicked by Yoda1, a specific activator of mechanosensitive calcium channel PIEZO1. PIEZO1 protein expression was upregulated by IR in vivo and in vitro. The increased PIEZO1 expression after IR was accompanied with increased calcium influx and increased calpain

SUBMITTER: Guo XW 

PROVIDER: S-EPMC8458942 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature