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• W4225383721 endingPage "113595" @default.
• W4225383721 startingPage "113595" @default.
• W4225383721 abstract "The goal of this study was to analyze whether mitochondria-associated endoplasmic reticulum membrane (MAMs) dysfunction mediated arsenic (As)-evoked pulmonary ferroptosis and acute lung injury (ALI). As exposure led to alveolar structure damage, inflammatory cell infiltration and pulmonary function decline in mice. Ferritin, the marker of iron overload, was increased, GPX4, the index of lipid peroxidation, was decreased in As-exposed lungs and pulmonary epithelial cells (MLE-12). Pretreatment with ferrostatin-1 (Fer-1), the inhibitor of ferroptosis, alleviated As-evoked ALI. In addition, As-induced non-heme iron deposition was inhibited in Fer-1 pretreated-mice. Moreover, As-triggered mitochondria damage and ferroptosis were mitigated in Fer-1 pretreated-MLE-12 cells. Mechanistically, PERK phosphorylation and mitofusin-2 (Mfn-2) reduction was observed in As-exposed MLE-12 cells and mice lungs. Additionally, the interaction between PERK and Mfn-2 was downregulated and MAMs dysfunction was observed in As-exposed MLE-12 cells. Intriguingly, PERK inhibitor and Mfn-2-overexpression all mitigated As-induced ferroptosis in MLE-12 cells. Additionally, CLPP and mtHSP70, the markers of mitochondrial stress, were upregulated, mitochondrial ROS (mtROS) was elevated, mitochondrial membrane potential (MMP) and ATP were decreased in As-exposed MLE-12 cells. Mitoquinone mesylate (MitoQ), a novel mitochondrial-targeted antioxidant, alleviated As-induced excess mtROS, mitochondrial stress, MAMs dysfunction in pulmonary epithelial cells. Similarly, in vivo experiments indicated that MitoQ pretreatment countered As-induced pulmonary ferroptosis and ALI. These data indicated that mtROS-initiated MAMs dysfunction is, at least partially, implicated in As-evoked ferroptosis and ALI." @default.
• W4225383721 created "2022-05-05" @default.
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• W4225383721 date "2022-06-01" @default.
• W4225383721 modified "2023-10-09" @default.
• W4225383721 title "Arsenic induces ferroptosis and acute lung injury through mtROS-mediated mitochondria-associated endoplasmic reticulum membrane dysfunction" @default.
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• W4225383721 doi "https://doi.org/10.1016/j.ecoenv.2022.113595" @default.
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