Work

DsbA-L deficiency promotes cigarette smoke-induced bronchial epithelial cells ferroptosis by inhibiting catalase in COPD

Year: 2024

Type: article

Abstract: Ferroptosis, characterized by iron-dependent programmed cell death, has been implicated in chronic obstructive pulmonary disease (COPD). Recent studies have shown that the disulfide-bond A oxidoreductase-like protein (DsbA-L) is associated with various diseases. However, the involvement of DsbA-L in COPD remains unclear. To establish a COPD model, 8-week-old male mice were exposed to cigarette smoke (CS) for 6 months. BEAS-2B cells were cultured with cigarette smoke extract (CSE) in vitro. DsbA-L siRNA, DsbA-L plasmid, or catalase siRNA were used to elucidate the underlying mechanisms. Lung function; lung histopathology; Fe 2+ concentration; glutathione (GSH), reactive oxygen species (ROS), 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) levels; and protein expression of DsbA-L, xCT, glutathione peroxidase-4 (GPX4), and catalase were measured. DsbA-L expression was significantly decreased in the lung tissues of COPD mice and CSE-treated BEAS-2B cells. DsbA-L knockout exacerbated COPD progression by increasing ferroptosis, as confirmed by reduced GSH, xCT, and GPX4 levels and elevated Fe 2+ , ROS, 4-HNE and MDA levels. Catalase expression was also attenuated in the lung tissues of COPD mice and CSE-treated BEAS-2B cells. DsbA-L overexpression ameliorated ferroptosis by upregulating catalase expression in BEAS-2B cells, whereas catalase knockdown abolished the effects of DsbA-L overexpression on ferroptosis. DsbA-L deficiency exacerbated COPD progression by promoting ferroptosis in bronchial epithelial cells through catalase inhibition. These findings indicate that DsbA-L may be an underlying therapeutic strategy for COPD. • DsbA-L was decreased in CS-exposed mice and CSE-treated cells. • DsbA-L deficiency exacerbated COPD progression by elevating ferroptosis. • DsbA-L overexpression inhibited bronchial epithelial cell ferroptosis via catalase.

Source: Environmental Technology & Innovation

DOI: 10.1016/j.eti.2024.103923

Authors: Siqi Li, Zhenyu Peng, Qiong Huang, Qiong Chen, Baimei He

Institutions: Central South University, Xiangya Hospital Central South University, Second Xiangya Hospital of Central South University

Language: English

Topic: Ferroptosis and cancer prognosis

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,440