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Hyperoxia Decreases Glycolytic Capacity, Glycolytic Reserve and Oxidative Phosphorylation in MLE-12 Cells and Inhibits Complex I and II Function, but Not Complex IV in Isolated Mouse Lung Mitochondria

High levels of oxygen (hyperoxia) are frequently used in critical care units and in conditions of respiratory insufficiencies in adults, as well as in infants. However, hyperoxia has been implicated in a number of pulmonary disorders including bronchopulmonary dysplasia (BPD) and adult respiratory d...

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Autor principal: Das, Kumuda C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759456/
https://www.ncbi.nlm.nih.gov/pubmed/24023862
http://dx.doi.org/10.1371/journal.pone.0073358
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author Das, Kumuda C.
author_facet Das, Kumuda C.
author_sort Das, Kumuda C.
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description High levels of oxygen (hyperoxia) are frequently used in critical care units and in conditions of respiratory insufficiencies in adults, as well as in infants. However, hyperoxia has been implicated in a number of pulmonary disorders including bronchopulmonary dysplasia (BPD) and adult respiratory distress syndrome (ARDS). Hyperoxia increases the generation of reactive oxygen species (ROS) in the mitochondria that could impair the function of the mitochondrial electron transport chain. We analyzed lung mitochondrial function in hyperoxia using the XF24 analyzer (extracellular flux) and optimized the assay for lung epithelial cells and mitochondria isolated from lungs of mice. Our data show that hyperoxia decreases basal oxygen consumption rate (OCR), spare respiratory capacity, maximal respiration and ATP turnover in MLE-12 cells. There was significant decrease in glycolytic capacity and glycolytic reserve in MLE-12 cells exposed to hyperoxia. Using mitochondria isolated from lungs of mice exposed to hyperoxia or normoxia we have shown that hyperoxia decreased the basal, state 3 and state3 μ (respiration in an uncoupled state) respirations. Further, using substrate or inhibitor of a specific complex we show that the OCR via complex I and II, but not complex IV was decreased, demonstrating that complexes I and II are specific targets of hyperoxia. Further, the activities of complex I (NADH dehydrogenase, NADH-DH) and complex II (succinate dehydrogenase, SDH) were decreased in hyperoxia, but the activity of complex IV (cytochrome oxidase, COX) remains unchanged. Taken together, our study show that hyperoxia impairs glycolytic and mitochondrial energy metabolism in in tact cells, as well as in lungs of mice by selectively inactivating components of electron transport system.
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spelling pubmed-37594562013-09-10 Hyperoxia Decreases Glycolytic Capacity, Glycolytic Reserve and Oxidative Phosphorylation in MLE-12 Cells and Inhibits Complex I and II Function, but Not Complex IV in Isolated Mouse Lung Mitochondria Das, Kumuda C. PLoS One Research Article High levels of oxygen (hyperoxia) are frequently used in critical care units and in conditions of respiratory insufficiencies in adults, as well as in infants. However, hyperoxia has been implicated in a number of pulmonary disorders including bronchopulmonary dysplasia (BPD) and adult respiratory distress syndrome (ARDS). Hyperoxia increases the generation of reactive oxygen species (ROS) in the mitochondria that could impair the function of the mitochondrial electron transport chain. We analyzed lung mitochondrial function in hyperoxia using the XF24 analyzer (extracellular flux) and optimized the assay for lung epithelial cells and mitochondria isolated from lungs of mice. Our data show that hyperoxia decreases basal oxygen consumption rate (OCR), spare respiratory capacity, maximal respiration and ATP turnover in MLE-12 cells. There was significant decrease in glycolytic capacity and glycolytic reserve in MLE-12 cells exposed to hyperoxia. Using mitochondria isolated from lungs of mice exposed to hyperoxia or normoxia we have shown that hyperoxia decreased the basal, state 3 and state3 μ (respiration in an uncoupled state) respirations. Further, using substrate or inhibitor of a specific complex we show that the OCR via complex I and II, but not complex IV was decreased, demonstrating that complexes I and II are specific targets of hyperoxia. Further, the activities of complex I (NADH dehydrogenase, NADH-DH) and complex II (succinate dehydrogenase, SDH) were decreased in hyperoxia, but the activity of complex IV (cytochrome oxidase, COX) remains unchanged. Taken together, our study show that hyperoxia impairs glycolytic and mitochondrial energy metabolism in in tact cells, as well as in lungs of mice by selectively inactivating components of electron transport system. Public Library of Science 2013-09-02 /pmc/articles/PMC3759456/ /pubmed/24023862 http://dx.doi.org/10.1371/journal.pone.0073358 Text en © 2013 Kumuda C http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Das, Kumuda C.
Hyperoxia Decreases Glycolytic Capacity, Glycolytic Reserve and Oxidative Phosphorylation in MLE-12 Cells and Inhibits Complex I and II Function, but Not Complex IV in Isolated Mouse Lung Mitochondria
title Hyperoxia Decreases Glycolytic Capacity, Glycolytic Reserve and Oxidative Phosphorylation in MLE-12 Cells and Inhibits Complex I and II Function, but Not Complex IV in Isolated Mouse Lung Mitochondria
title_full Hyperoxia Decreases Glycolytic Capacity, Glycolytic Reserve and Oxidative Phosphorylation in MLE-12 Cells and Inhibits Complex I and II Function, but Not Complex IV in Isolated Mouse Lung Mitochondria
title_fullStr Hyperoxia Decreases Glycolytic Capacity, Glycolytic Reserve and Oxidative Phosphorylation in MLE-12 Cells and Inhibits Complex I and II Function, but Not Complex IV in Isolated Mouse Lung Mitochondria
title_full_unstemmed Hyperoxia Decreases Glycolytic Capacity, Glycolytic Reserve and Oxidative Phosphorylation in MLE-12 Cells and Inhibits Complex I and II Function, but Not Complex IV in Isolated Mouse Lung Mitochondria
title_short Hyperoxia Decreases Glycolytic Capacity, Glycolytic Reserve and Oxidative Phosphorylation in MLE-12 Cells and Inhibits Complex I and II Function, but Not Complex IV in Isolated Mouse Lung Mitochondria
title_sort hyperoxia decreases glycolytic capacity, glycolytic reserve and oxidative phosphorylation in mle-12 cells and inhibits complex i and ii function, but not complex iv in isolated mouse lung mitochondria
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759456/
https://www.ncbi.nlm.nih.gov/pubmed/24023862
http://dx.doi.org/10.1371/journal.pone.0073358
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