Metabolic re-patterning in COPD airway smooth muscle cells.
Metabolic re-patterning in COPD airway smooth muscle cells.
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DOI：
10.1183/13993003.00202-2017
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
COPDMAP
中科院分区：
文献类型：
--
作者：
Michaeloudes C;Kuo CH;Haji G;Finch DK;Halayko AJ;Kirkham P;Chung KF;Adcock IM;COPDMAP
慢性阻塞性肺疾病（COPD）气道的特征是气道平滑肌增厚，部分原因是气道平滑肌细胞（ASMC）增生。代谢重编程涉及增加糖酵解和谷氨酰胺分解代谢，支持细胞生长所需的生物合成和氧化还原平衡。我们研究了COPD ASMCs是否表现出可能促进生长的独特代谢表型。我们在未刺激或生长的转化生长因子(TGF)-β和胎牛血清（FBS）条件下，对健康非吸烟者、健康吸烟者和COPD患者的ASMCs进行了探索性的细胞内代谢谱分析。与未刺激和生长条件下的对照组相比，COPD ASMCs表现出能量平衡受损，糖酵解产物乳酸、谷氨酰胺、脂肪酸和氨基酸的积累受损。在无刺激条件下，脂肪酸氧化能力降低。TGF-β/ fbs刺激的COPD ASMCs显示脂肪酸氧化能力恢复，戊糖磷酸途径产物核糖-5-磷酸和核苷酸生物合成中间体上调，谷氨酰胺分解代谢物谷氨酸水平升高。此外，TGF-β/ fbs刺激的COPD ASMCs显示出更高的还原-氧化谷胱甘肽比率和更低的线粒体氧化剂水平。抑制糖酵解和谷氨酰胺耗竭可减弱TGF-β/ fbs刺激的COPD ASMCs生长。糖酵解、谷氨酰胺和脂肪酸代谢的变化可能导致生物合成和氧化还原平衡的增加，支持COPD ASMC的生长。COPD患者气道平滑肌细胞的代谢变化可能支持其生长和生存http://ow.ly/XVkb30eUTLJ
Chronic obstructive pulmonary disease (COPD) airways are characterised by thickening of airway smooth muscle, partly due to airway smooth muscle 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 nonsmokers, 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, upregulation of the pentose phosphate pathway product ribose-5-phosphate and of nucleotide biosynthesis intermediates, and increased levels of the glutamine catabolite glutamate. In addition, TGF-β/FBS-stimulated COPD ASMCs 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. A metabolic shift in airway smooth muscle cells of COPD patients may support their increased growth and survival http://ow.ly/XVkb30eUTLJ
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影响因子：
82.9
作者：
Cloonan SM;Glass K;Laucho-Contreras ME;Bhashyam AR;Cervo M;Pabón MA;Konrad C;Polverino F;Siempos II;Perez E;Mizumura K;Ghosh MC;Parameswaran H;Williams NC;Rooney KT;Chen ZH;Goldklang MP;Yuan GC;Moore SC;Demeo DL;Rouault TA;D'Armiento JM;Schon EA;Manfredi G;Quackenbush J;Mahmood A;Silverman EK;Owen CA;Choi AM
通讯作者：
Choi AM
DOI：
10.1513/pats.200504-028sr
发表时间：
2005-01-01
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
Chung, Kian Fan
通讯作者：
Chung, Kian Fan
DOI：
10.1164/rccm.201011-1780oc
发表时间：
2011-10-15
影响因子：
24.7
作者：
Michaeloudes, Charalambos;Chang, Po-Jui;Chung, Kian Fan
通讯作者：
Chung, Kian Fan
影响因子：
15.9
作者：
Mizumura, Kenji;Cloonan, Suzanne M.;Choi, Augustine M. K.
通讯作者：
Choi, Augustine M. K.
影响因子：
64.8
作者：
Metallo, Christian M.;Gameiro, Paulo A.;Bell, Eric L.;Mattaini, Katherine R.;Yang, Juanjuan;Hiller, Karsten;Jewell, Christopher M.;Johnson, Zachary R.;Irvine, Darrell J.;Guarente, Leonard;Kelleher, Joanne K.;Vander Heiden, Matthew G.;Iliopoulos, Othon;Stephanopoulos, Gregory
通讯作者：
Stephanopoulos, Gregory