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Toxicology and applied pharmacology

Toxicology and applied pharmacology

IF: 3.3
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PM2.5 enhances DRP1-mediated mitochondrial fission to induce ferroptosis and exacerbate asthma through the AHR-HSP90-PKM2 pathway

Published:4 October 2025 DOI: 10.1016/j.taap.2025.117590 PMID: 41052681
Simiao Qiao , Fanshu Li , Jia Huang , Xiaoqian Wu , Xiaoying Cao , Xifeng Zhang , Zhifeng Wei

Abstract

This study was designed to clarify the reason for PM2.5 to induce the ferroptosis of bronchial epithelial cells and worsen asthma in detail, advancing the development of relevant drugs. Results displayed that PM2.5 mainly induced ferroptosis but not apoptosis of bronchial epithelial cells, indicating by the changes of lipid reactive oxygen species (ROS), iron, malondialdehyde, lactic dehydrogenase, nuclear receptor coactivator 4, glutathione and glutathione peroxidase 4 levels, and further confirmed by using in combination with the ferroptosis and apoptosis inhibitors. It also caused the mitochondrial disturbance, reduced the level of mitochondrial membrane potential, up-regulated the level of mitochondrial ROS, and mechanisms were subsequently ascribed to dynamin-related protein 1 (DRP1)-related mitochondrial fission. Furthermore, the up-regulation on ubiquitination of pyruvate kinase M2 (PKM2) but not macrophage stimulating 1 or interferon regulatory factor 1, the transcriptional regulators locating at the upstream of DRP1, was showed by PM2.5 via controlling “aryl hydrocarbon receptor (AHR)-heat shock protein 90 (HSP90)” axis. In addition, isoliquiritigenin (ISL), the main active ingredients in licorice, was demonstrated to prevent the PM2.5-induced activation of AHR-PKM2-ferroptosis in asthma. In conclusion, PM2.5 activated “AHR-HSP90” axis to disturb DRP1-related mitochondrial fission, induced ferroptosis of bronchial epithelial cells, and worsened asthma. Conversely, ISL restored the above-mentioned signals, ferroptosis and asthma mediated by PM2.5, and was suggested as a potential compound to combat the exacerbation of asthma.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
2-[1-[4-[2-(4-Chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone 571203-78-6 C30H31ClN4O4 284 suppliers $16.00-$2691.10
2-[1-[4-[2-(4-Chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone 571203-78-6 C30H31ClN4O4 284 suppliers $16.00-$2691.10
2-[1-[4-[2-(4-Chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone 571203-78-6 C30H31ClN4O4 284 suppliers $16.00-$2691.10
2-[1-[4-[2-(4-Chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone 571203-78-6 C30H31ClN4O4 284 suppliers $16.00-$2691.10

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