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Ceramide and sphingosine-1 phosphate in COPD lungs
Evgeny V Berdyshev1,2, Karina A Serban1,3,4, Kelly S Schweitzer1,3
1Department of Medicine, National Jewish Health, Denver, Colorado, USA.
Chronic obstructive pulmonary disease (COPD) involves altered sphingolipid metabolism in the lungs. Disrupted ceramide and sphingosine-1 phosphate (S1P) balance contributes to emphysema in COPD patients.
Area of Science:
- Pulmonary Medicine
- Biochemistry
- Cell Biology
Background:
- Sphingolipid metabolism is dysregulated in chronic obstructive pulmonary disease (COPD) based on animal and plasma studies.
- However, data regarding sphingolipid metabolism specifically within COPD lungs remain limited.
Purpose of the Study:
- To investigate the role of sphingolipid metabolism, specifically ceramide and sphingosine-1 phosphate (S1P) levels and sphingosine kinase-1 (SphK1) activity, in the lungs of COPD patients.
- To correlate these metabolic changes with disease severity and emphysema phenotype.
Main Methods:
- Mass spectrometry and immunostaining techniques were employed.
- Lung tissue samples were analyzed from 69 COPD patients, 16 smokers without COPD, and 13 individuals with interstitial lung disease.
Main Results:
- A decoupling of ceramide and sphingosine-1 phosphate (S1P) levels was observed in COPD lungs.
- Decreased sphingosine kinase-1 (SphK1) activity was identified in COPD lungs.
- Increased ceramide in distal COPD lungs correlated with apoptosis, while SphK1 activity inversely correlated with emphysema presence.
Conclusions:
- Disruption of the ceramide-to-S1P metabolic pathway is implicated in the pathogenesis of COPD.
- This metabolic imbalance is a significant determinant of the emphysema phenotype observed in COPD.
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