[Cited FineTest ELISA Kit] Current Research on Chronic Obstructive Pulmonary Disease

FineTest ELISA kit contributes to the research on chronic obstructive pulmonary disease. The immunoassay is designed to measure 8-epi-PGF2α level in BEAS-2b cells and lung tissues.

Article Title: Lipid peroxidation triggered by the degradation of xCT contributes to gasdermin D-mediated pyroptosis in COPD
Journal Title: Redox Biology
DOI: 10.1016/j.redox.2024.103388
IF: 10.7
PMID: 39374556

Abstract: Background Pyroptosis is an inflammatory form of regulated necrosis that has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the role of lipid peroxidation in pyroptosis and its underlying mechanisms in COPD remain unclear. Methods In vitro, human bronchial epithelial cells (Beas-2b cells) were exposed to cigarette smoke extract (CSE) for 24 h. In vivo, mice were exposed to cigarette smoke (CS) for 4 weeks. To investigate the role of xCT, we used siRNA and AAV6 to conditionally knock down xCT in vitro and in vivo, respectively. Results The administration of ferrostatin-1 (Fer-1), a ferroptosis inhibitor that inhibits lipid peroxidation, significantly reduced the cytotoxicity of CSE to Beas-2b cells and mitigated inflammatory exudation, lung injury and mucus hypersecretion in mice with CS-induced COPD. Fer-1 suppressed gasdermin D (GSDMD)-mediated pyroptosis caused by CS in vitro and in vivo. However, in Beas-2b cells and the lung epithelial cells of mice, conditional knockdown of xCT (a negative regulatory factor of lipid peroxidation) inhibited the xCT/GPx4 axis, leading to more severe lipid peroxidation and GSDMD-mediated pyroptosis during cigarette smoke exposure. Moreover, we found that CS promoted the degradation of xCT through the ubiquitin proteasome system (UPS) and that treatment with MG132 significantly inhibited the degradation of xCT and downregulated the expression of pyroptosis-related proteins. Conclusion The results of this study suggested that the ubiquitination-mediated degradation of xCT drives GSDMD-mediated pyroptosis in COPD and is a potential therapeutic target for COPD.

Keywords: Lipid peroxidation, xCT, Pyroptosis, Chronic Obstructive Pulmonary Disease(COPD)

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Figure Source: Redox Biol. 2024 Oct 3:77:103388. doi: 10.1016/j.redox.2024.103388.