2.50
Hdl Handle:
http://hdl.handle.net/2436/620654
Title:
Metabolic re-patterning in chronic obstructive pulmonary disease airway smooth muscle cells
Authors:
Michaeloudes, Charalambos; Kuo, Chih-Hsi; Haji, Gulam; Finch, Donna; Halayko, Andrew J; Kirkham, Paul; Chung, Kian Fan; Adcock, Ian M
Abstract:
COPD 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.
Publisher:
European Respiratory Society
Journal:
European Respiratory Journal
Issue Date:
30-Nov-2017
URI:
http://hdl.handle.net/2436/620654
Additional Links:
http://erj.ersjournals.com/lookup/doi/10.1183/13993003.00202-2017
Type:
Article
Language:
en
ISSN:
0903-193
Sponsors:
MRC-ABPI COPDMAP consortium G1001367/1
Appears in Collections:
School of Biomedical Sciences and Physiology

Full metadata record

DC FieldValue Language
dc.contributor.authorMichaeloudes, Charalambosen
dc.contributor.authorKuo, Chih-Hsien
dc.contributor.authorHaji, Gulamen
dc.contributor.authorFinch, Donnaen
dc.contributor.authorHalayko, Andrew Jen
dc.contributor.authorKirkham, Paulen
dc.contributor.authorChung, Kian Fanen
dc.contributor.authorAdcock, Ian Men
dc.date.accessioned2017-09-07T14:35:05Z-
dc.date.available2017-09-07T14:35:05Z-
dc.date.issued2017-11-30-
dc.identifier.issn0903-193en
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.en
dc.description.sponsorshipMRC-ABPI COPDMAP consortium G1001367/1en
dc.language.isoenen
dc.publisherEuropean Respiratory Societyen
dc.relation.urlhttp://erj.ersjournals.com/lookup/doi/10.1183/13993003.00202-2017en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectCOPDen
dc.subjectMetabonomicsen
dc.subjectGlycolysisen
dc.subjectpentose phosphate pathwayen
dc.subjectmetabolismen
dc.titleMetabolic re-patterning in chronic obstructive pulmonary disease airway smooth muscle cellsen
dc.typeArticleen
dc.identifier.journalEuropean Respiratory Journalen
dc.date.accepted2017-08-
rioxxterms.funderMRC-ABPI COPDMAP consortiumen
rioxxterms.identifier.projectG1001367/1en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttps://creativecommons.org/CC BY-NC-ND 4.0en
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