2. Academic Validation
  3. The cuproptosis-related gene glutaminase promotes alveolar macrophage copper ion accumulation in chronic obstructive pulmonary disease

The cuproptosis-related gene glutaminase promotes alveolar macrophage copper ion accumulation in chronic obstructive pulmonary disease

  • Int Immunopharmacol. 2024 Mar 10:129:111585. doi: 10.1016/j.intimp.2024.111585.
Linxiao Han 1,  Wensi Zhu 1,  Hui Qi 2,  Ludan He 3,  Qin Wang 1,  Jie Shen 4,  Yuanlin Song 5,  Yao Shen 6,  Qiaoliang Zhu 7,  Jian Zhou 8
Affiliations

Affiliations

  • 1 Department of Pulmonary and Critical Care Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Engineering Research Center of Internet of Things for Respiratory Medicine, 180 Fenglin Road, Shanghai 200032, China; Shanghai Key Laboratory of Lung Inflammation and Injury, 180 Fenglin Road, Shanghai 200032, China.
  • 2 Hebei Academy of Integrated Traditional Chinese and Western Medicine, Shijiazhuang 050091, Hebei, China.
  • 3 Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China; Shanghai Engineering Research Center of Internet of Things for Respiratory Medicine, 180 Fenglin Road, Shanghai 200032, China; Shanghai Key Laboratory of Lung Inflammation and Injury, 180 Fenglin Road, Shanghai 200032, China.
  • 4 Research Center for Chemical Injury, Emergency and Critical Medicine of Fudan University, Fudan University, Shanghai 200540, China; Center of Emergency and Critical Medicine in Jinshan Hospital of Fudan University, Fudan University, Shanghai 200540, China; Key Laboratory of Chemical Injury, Emergency and Critical Medicine of Shanghai Municipal Health Commission, Shanghai 200540, China.
  • 5 Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Lung Inflammation and Injury, 180 Fenglin Road, Shanghai 200032, China.
  • 6 Department of Respiratory and Critical Care Medicine, Shanghai Pudong Hospital, Shanghai 201399, China. Electronic address: [email protected].
  • 7 Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China. Electronic address: [email protected].
  • 8 Department of Pulmonary and Critical Care Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Engineering Research Center of Internet of Things for Respiratory Medicine, 180 Fenglin Road, Shanghai 200032, China; Shanghai Key Laboratory of Lung Inflammation and Injury, 180 Fenglin Road, Shanghai 200032, China; Hebei Academy of Integrated Traditional Chinese and Western Medicine, Shijiazhuang 050091, Hebei, China; Research Center for Chemical Injury, Emergency and Critical Medicine of Fudan University, Fudan University, Shanghai 200540, China; Center of Emergency and Critical Medicine in Jinshan Hospital of Fudan University, Fudan University, Shanghai 200540, China; Key Laboratory of Chemical Injury, Emergency and Critical Medicine of Shanghai Municipal Health Commission, Shanghai 200540, China. Electronic address: [email protected].
PMID: 38325045 DOI: 10.1016/j.intimp.2024.111585
Abstract

Cuproptosis, a novel mode of cell death, is strongly associated with a variety of diseases. However, the contribution of cuproptosis to the onset or progression of chronic obstructive pulmonary disease (COPD), the third most common chronic cause of mortality, is not yet clear. To investigate the potential role of cuproptosis in COPD, raw datasets from multiple public clinical COPD databases (including RNA-seq, phenotype, and lung function data) were used. For further validation, mice exposed to cigarette smoke for three months were used as in vivo models, and iBMDMs (immortalized bone marrow-derived macrophages) and RAW264.7 cells stimulated with cigarette smoke extract were used as in vitro models. For the first time, the expression of the cuproptosis-related gene Glutaminase (GLS) was found to be decreased in COPD, and the low expression of GLS was significantly associated with the grade of pulmonary function. In vivo experiments confirmed the decreased expression of GLS in COPD, particularly in alveolar macrophages. Furthermore, in vitro studies revealed that copper ions accumulated in alveolar macrophages, leading to a substantially decreased amount of cell activity of macrophages when stimulated with cigarette extract. In summary, we demonstrate the high potential of GLS as an avenue for diagnosis and therapy in COPD.

Keywords

Alveolar macrophage; COPD; Cuproptosis; GLS; Smoke.

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