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CSE triggers ferroptosis via SIRT4-mediated GNPAT deacetylation in the pathogenesis of COPD.
Li, Congping; Chen, Fei; Lin, Liangfen; Li, Jiwei; Zheng, Yamei; Chen, Qingyun.
Afiliação
  • Li C; Pulmonary and Critical Care Medicine, Hainan Affiliated Hospital of Hainan Medical University, Haikou City, Hainan Province, 570311, China.
  • Chen F; Department of Laboratory, AffIliated to Shanghai Jiao Tong University School of Medicine Shanghai Children's Medical Center, Hainan Branch, Sanya City, Hainan Province, 572000, China.
  • Lin L; Pulmonary and Critical Care Medicine, DingAn People's Hospital, Dingan City, Hainan Province, 571200, China.
  • Li J; Pulmonary and Critical Care Medicine, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), No.19 Xiuhua Road, Xiuying District, Haikou City, Hainan Province, 570311, China.
  • Zheng Y; Pulmonary and Critical Care Medicine, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), No.19 Xiuhua Road, Xiuying District, Haikou City, Hainan Province, 570311, China.
  • Chen Q; Pulmonary and Critical Care Medicine, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), No.19 Xiuhua Road, Xiuying District, Haikou City, Hainan Province, 570311, China. chenqingyun@hainmc.edu.cn.
Respir Res ; 24(1): 301, 2023 Dec 01.
Article em En | MEDLINE | ID: mdl-38041059
BACKGROUND: It is now understood that ferroptosis plays a significant role in the progression of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke extract (CSE). However, the mechanisms underlying this relationship remain largely unclear. METHODS: In this study, we established a COPD mouse model through exposure to cigarette smoke particulates, followed by H&E staining, analysis of bronchoalveolar lavage fluid, and immunohistochemistry assay. A549 cells were exposed to increasing concentrations of CSE, with the addition of the ferroptosis activator erastin or the inhibitor Fer-1. Cell viability, LDH (lactate dehydrogenase) release, inflammatory cytokines, total ROS (reactive oxygen species), and lipid ROS were measured using the corresponding assay kits. The acetylation level of GNPAT was determined through immunoprecipitation. We assessed the expression levels of molecules involved in plasmalogen biosynthesis (FAR1, AGPS, and GNPAT), GPX4, and SIRT4 using quantitative real-time PCR, western blot analysis, and immunofluorescence staining. RESULTS: CSE-induced lung tissue damage was initially observed, accompanied by oxidative stress, ferroptosis, and increased plasmalogen biosynthesis molecules (FAR1, AGPS, and GNPAT). CSE also induced ferroptosis in A549 cells, resulting in reduced cell viability, GSH, and GPX4 levels, along with increased LDH, ROS, MDA (malondialdehyde) levels, oxidized lipids, and elevated FAR1, AGPS, and GNPAT expression. Knockdown of GNPAT mitigated CSE-induced ferroptosis. Furthermore, we found that CSE regulated the acetylation and protein levels of GNPAT by modulating SIRT4 expression. Importantly, the overexpression of GNPAT countered the inhibitory effects of SIRT4 on ferroptosis. CONCLUSIONS: Our study revealed GNPAT could be deacetylated by SIRT4, providing novel insights into the mechanisms underlying the relationship between CSE-induced ferroptosis and COPD.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença Pulmonar Obstrutiva Crônica / Ferroptose Limite: Animals Idioma: En Revista: Respir Res Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença Pulmonar Obstrutiva Crônica / Ferroptose Limite: Animals Idioma: En Revista: Respir Res Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China