Proteome Profiling of Red Blood Cells from Patients with COPD Links Proteasome Activation with Abnormal Cell Morphology and Function.

Introduction: Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and persistent respiratory symptoms. Molecular and cellular changes identified in red blood cells (RBCs) of COPD patients may contribute to the pathophysiology of COPD, impacting oxygen transport and systemic inflammation.

Methods: We performed a comparative proteomic analysis on RBCs from 15 male COPD patients and 15 age- and sex-matched control subjects. For the proteomic analysis, individual samples were randomly pooled into 3 biological replicates per group (n = 3). Total RBC proteins were analyzed using tandem mass tag (TMT) labeling followed by LC-MS/MS. Differentially abundant proteins (DAPs) were identified and subjected to Gene Ontology (GO), KEGG pathway, and protein-protein interaction (PPI) network analyses.

Results: We identified 160 DAPs (70 up-regulated, 90 down-regulated) in the RBCs of COPD patients. GO analysis revealed enrichment in processes related to protein stability regulation and immune response. KEGG pathway analysis showed that up-regulated proteins were most significantly enriched in the proteasome pathway, while down-regulated proteins were enriched in complement and coagulation cascades. Notably, a PPI network analysis highlighted a core complex of 10 up-regulated proteins that are all components of the proteasome regulatory particle.

Conclusion: This study provides the in-depth RBC protein profile in COPD, identifying proteasome activation as a key molecular signature. These findings reveal novel biomarkers linked to RBC dysfunction that may contribute to the systemic pathology of COPD and offer potential new therapeutic targets.