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dc.contributor.authorMichaeloudes, Charalambos
dc.contributor.authorKuo, Chih-Hsi
dc.contributor.authorHaji, Gulam
dc.contributor.authorFinch, Donna
dc.contributor.authorHalayko, Andrew J
dc.contributor.authorKirkham, Paul
dc.contributor.authorChung, Kian Fan
dc.contributor.authorAdcock, Ian M
dc.date.accessioned2017-09-07T14:35:05Z
dc.date.available2017-09-07T14:35:05Z
dc.date.issued2017-11-30
dc.identifier.citationMichaeloudes C., Kuo CH., Haji G., Finch DK., Halayko AJ., Kirkham P., Chung KF., Adcock IM. Metabolic re-patterning in COPD airway smooth muscle cells, European Respiratory Journal, 50(5) doi: 10.1183/13993003.00202
dc.identifier.issn0903-193
dc.identifier.doi10.1183/13993003.00202-2017
dc.identifier.urihttp://hdl.handle.net/2436/620654
dc.description.abstractCOPD airways are characterised by airway smooth muscle (ASM) thickening, partly due to ASM cell (ASMC) hyperplasia. Metabolic reprogramming involving increased glycolysis and glutamine catabolism supports the biosynthetic and redox balance required for cellular growth. We examined whether COPD ASMCs show a distinct metabolic phenotype that may contribute to increased growth. We performed an exploratory intracellular metabolic profile analysis of ASMCs from healthy non-smokers, healthy smokers and COPD patients, under unstimulated or growth conditions of transforming growth factor (TGF)-β and fetal bovine serum (FBS). COPD ASMCs showed impaired energy balance and accumulation of the glycolytic product lactate, glutamine, fatty acids and amino acids compared to controls in unstimulated and growth conditions. Fatty acid oxidation capacity was reduced under unstimulated conditions. TGF-β/FBS-stimulated COPD ASMCs showed restoration of fatty acid oxidation capacity, up-regulation of the pentose phosphate pathway product ribose-5- phosphate and of nucleotide biosynthesis intermediates, and increased levels of the glutamine catabolite glutamate. TGF-β/FBS-stimulated COPD ASMCs also showed a higher reduced to oxidised glutathione ratio and lower mitochondrial oxidant levels. Inhibition of glycolysis, and glutamine depletion attenuated TGF-β/FBS-stimulated growth of COPD ASMCs. Changes in glycolysis, glutamine and fatty acid metabolism may lead to increased biosynthesis and redox balance, supporting COPD ASMC growth.
dc.description.sponsorshipMRC-ABPI COPDMAP consortium G1001367/1
dc.language.isoen
dc.publisherEuropean Respiratory Society
dc.relation.urlhttp://erj.ersjournals.com/lookup/doi/10.1183/13993003.00202-2017
dc.subjectCOPD
dc.subjectMetabonomics
dc.subjectGlycolysis
dc.subjectpentose phosphate pathway
dc.subjectmetabolism
dc.titleMetabolic re-patterning in chronic obstructive pulmonary disease airway smooth muscle cells
dc.typeJournal article
dc.identifier.journalEuropean Respiratory Journal
dc.date.accepted2017-08-31
rioxxterms.funderUniversity of Wolverhampton
rioxxterms.identifier.projectG1001367/1
rioxxterms.versionAM
rioxxterms.licenseref.urihttps://creativecommons.org/CC BY-NC-ND 4.0
dc.source.volume50
dc.source.issue5
refterms.dateFCD2018-10-19T09:26:31Z
refterms.versionFCDAM
html.description.abstractCOPD airways are characterised by airway smooth muscle (ASM) thickening, partly due to ASM cell (ASMC) hyperplasia. Metabolic reprogramming involving increased glycolysis and glutamine catabolism supports the biosynthetic and redox balance required for cellular growth. We examined whether COPD ASMCs show a distinct metabolic phenotype that may contribute to increased growth. We performed an exploratory intracellular metabolic profile analysis of ASMCs from healthy non-smokers, healthy smokers and COPD patients, under unstimulated or growth conditions of transforming growth factor (TGF)-β and fetal bovine serum (FBS). COPD ASMCs showed impaired energy balance and accumulation of the glycolytic product lactate, glutamine, fatty acids and amino acids compared to controls in unstimulated and growth conditions. Fatty acid oxidation capacity was reduced under unstimulated conditions. TGF-β/FBS-stimulated COPD ASMCs showed restoration of fatty acid oxidation capacity, up-regulation of the pentose phosphate pathway product ribose-5- phosphate and of nucleotide biosynthesis intermediates, and increased levels of the glutamine catabolite glutamate. TGF-β/FBS-stimulated COPD ASMCs also showed a higher reduced to oxidised glutathione ratio and lower mitochondrial oxidant levels. Inhibition of glycolysis, and glutamine depletion attenuated TGF-β/FBS-stimulated growth of COPD ASMCs. Changes in glycolysis, glutamine and fatty acid metabolism may lead to increased biosynthesis and redox balance, supporting COPD ASMC growth.


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