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Conlon, T.M. ; Bartel, J. ; Ballweg, K. ; Günter, S. ; Prehn, C. ; Krumsiek, J. ; Meiners, S. ; Theis, F.J. ; Adamski, J. ; Eickelberg, O. ; Yildirim, A.Ö.

Metabolomics screening identifies reduced L-carnitine to be associated with progressive emphysema.

Clin. Sci. 130, 273-287 (2016)
Verlagsversion Postprint DOI PMC
Open Access Gold
Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, small airway remodeling and emphysema. Emphysema is the destruction of alveolar structures, leading to enlarged airspaces and reduced surface area impairing the ability for gaseous exchange. To further understand the pathological mechanisms underlying progressive emphysema we used mass spectrometry-based approaches to quantitate the lung, bronchoalveolar-lavage fluid (BALF) and serum metabolome during emphysema progression in the established murine porcine pancreatic elastase (PPE) model on days 28, 56 and 161, compared to PBS controls. Partial Least Square analysis revealed greater changes in the metabolome of lung followed by BALF rather than serum during emphysema progression. Furthermore, we demonstrate for the first time that emphysema progression is associated with a reduction in lung specific L-carnitine, a metabolite critical for transporting long chain fatty acids into the mitochondria for their subsequent β-oxidation. In vitro , stimulation of the ATII-like LA4 cell line with L-carnitine diminished apoptosis induced by both PPE and H2O2. Moreover, PPE-treated mice demonstrated impaired lung function compared to PBS treated controls (lung compliance; 0.067±0.008ml/cmH20 vs 0.035±0.005ml/cmH20, p<0.0001), which improved following supplementation with L-carnitine (0.051±0.006, p<0.01) and was associated with a reduction in apoptosis. In summary, our results provide a new insight into the role of L-carnitine and, importantly, suggest therapeutic avenues for COPD.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Apoptosis ; Biomarkers ; Chronic Obstructive Pulmonary Disease (copd) ; Metabolome; Obstructive Pulmonary-disease; Elastase-induced Emphysema; Endothelial Growth-factor; Cytochrome-c Release; Epithelial-cells; Permeability Transition; Mitochondrial-function; Oxidative Stress; Lung Surfactant; Apoptosis
Sprache englisch
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 0143-5221
e-ISSN 0143-5221
Zeitschrift Clinical Science
Quellenangaben Band: 130, Heft: 4, Seiten: 273-287 Artikelnummer: , Supplement: ,
Verlag Portland Press
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Lung Health and Immunity (LHI)
Institute of Computational Biology (ICB)
Molekulare Endokrinologie und Metabolismus (MEM)
Institute of Experimental Genetics (IEG)
POF Topic(s) 30202 - Environmental Health
30205 - Bioengineering and Digital Health
30201 - Metabolic Health
90000 - German Center for Diabetes Research
Forschungsfeld(er) Lung Research
Enabling and Novel Technologies
Genetics and Epidemiology
PSP-Element(e) G-505000-007
G-503800-001
G-501600-004
G-501600-001
G-505600-003
G-505000-006
G-501900-061
DOI 10.1042/CS20150438
WOS ID WOS:000369718200006
Scopus ID 84958045017
PubMed ID 26564208
Erfassungsdatum 2015-11-15
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