High CO2 levels impair alveolar epithelial function independently of pH.
In patients with acute respiratory failure, gas exchange is impaired due to the accumulation of fluid in the lung airspaces. This life-threatening syndrome is treated with mechanical ventilation, which is adjusted to maintain gas exchange, but can be associated with the accumulation of carbon dioxid...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2007-11-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2077933?pdf=render |
| _version_ | 1819010379246731264 |
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| author | Arturo Briva István Vadász Emilia Lecuona Lynn C Welch Jiwang Chen Laura A Dada Humberto E Trejo Vidas Dumasius Zaher S Azzam Pavlos M Myrianthefs Daniel Batlle Yosef Gruenbaum Jacob I Sznajder |
| author_facet | Arturo Briva István Vadász Emilia Lecuona Lynn C Welch Jiwang Chen Laura A Dada Humberto E Trejo Vidas Dumasius Zaher S Azzam Pavlos M Myrianthefs Daniel Batlle Yosef Gruenbaum Jacob I Sznajder |
| author_sort | Arturo Briva |
| collection | DOAJ |
| description | In patients with acute respiratory failure, gas exchange is impaired due to the accumulation of fluid in the lung airspaces. This life-threatening syndrome is treated with mechanical ventilation, which is adjusted to maintain gas exchange, but can be associated with the accumulation of carbon dioxide in the lung. Carbon dioxide (CO2) is a by-product of cellular energy utilization and its elimination is affected via alveolar epithelial cells. Signaling pathways sensitive to changes in CO2 levels were described in plants and neuronal mammalian cells. However, it has not been fully elucidated whether non-neuronal cells sense and respond to CO2. The Na,K-ATPase consumes approximately 40% of the cellular metabolism to maintain cell homeostasis. Our study examines the effects of increased pCO2 on the epithelial Na,K-ATPase a major contributor to alveolar fluid reabsorption which is a marker of alveolar epithelial function.We found that short-term increases in pCO2 impaired alveolar fluid reabsorption in rats. Also, we provide evidence that non-excitable, alveolar epithelial cells sense and respond to high levels of CO2, independently of extracellular and intracellular pH, by inhibiting Na,K-ATPase function, via activation of PKCzeta which phosphorylates the Na,K-ATPase, causing it to endocytose from the plasma membrane into intracellular pools.Our data suggest that alveolar epithelial cells, through which CO2 is eliminated in mammals, are highly sensitive to hypercapnia. Elevated CO2 levels impair alveolar epithelial function, independently of pH, which is relevant in patients with lung diseases and altered alveolar gas exchange. |
| first_indexed | 2024-12-21T01:11:19Z |
| format | Article |
| id | doaj.art-92fe4de1ced84bc289b8a41251daedf3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T01:11:19Z |
| publishDate | 2007-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-92fe4de1ced84bc289b8a41251daedf32022-12-21T19:20:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-11-01211e123810.1371/journal.pone.0001238High CO2 levels impair alveolar epithelial function independently of pH.Arturo BrivaIstván VadászEmilia LecuonaLynn C WelchJiwang ChenLaura A DadaHumberto E TrejoVidas DumasiusZaher S AzzamPavlos M MyrianthefsDaniel BatlleYosef GruenbaumJacob I SznajderIn patients with acute respiratory failure, gas exchange is impaired due to the accumulation of fluid in the lung airspaces. This life-threatening syndrome is treated with mechanical ventilation, which is adjusted to maintain gas exchange, but can be associated with the accumulation of carbon dioxide in the lung. Carbon dioxide (CO2) is a by-product of cellular energy utilization and its elimination is affected via alveolar epithelial cells. Signaling pathways sensitive to changes in CO2 levels were described in plants and neuronal mammalian cells. However, it has not been fully elucidated whether non-neuronal cells sense and respond to CO2. The Na,K-ATPase consumes approximately 40% of the cellular metabolism to maintain cell homeostasis. Our study examines the effects of increased pCO2 on the epithelial Na,K-ATPase a major contributor to alveolar fluid reabsorption which is a marker of alveolar epithelial function.We found that short-term increases in pCO2 impaired alveolar fluid reabsorption in rats. Also, we provide evidence that non-excitable, alveolar epithelial cells sense and respond to high levels of CO2, independently of extracellular and intracellular pH, by inhibiting Na,K-ATPase function, via activation of PKCzeta which phosphorylates the Na,K-ATPase, causing it to endocytose from the plasma membrane into intracellular pools.Our data suggest that alveolar epithelial cells, through which CO2 is eliminated in mammals, are highly sensitive to hypercapnia. Elevated CO2 levels impair alveolar epithelial function, independently of pH, which is relevant in patients with lung diseases and altered alveolar gas exchange.http://europepmc.org/articles/PMC2077933?pdf=render |
| spellingShingle | Arturo Briva István Vadász Emilia Lecuona Lynn C Welch Jiwang Chen Laura A Dada Humberto E Trejo Vidas Dumasius Zaher S Azzam Pavlos M Myrianthefs Daniel Batlle Yosef Gruenbaum Jacob I Sznajder High CO2 levels impair alveolar epithelial function independently of pH. PLoS ONE |
| title | High CO2 levels impair alveolar epithelial function independently of pH. |
| title_full | High CO2 levels impair alveolar epithelial function independently of pH. |
| title_fullStr | High CO2 levels impair alveolar epithelial function independently of pH. |
| title_full_unstemmed | High CO2 levels impair alveolar epithelial function independently of pH. |
| title_short | High CO2 levels impair alveolar epithelial function independently of pH. |
| title_sort | high co2 levels impair alveolar epithelial function independently of ph |
| url | http://europepmc.org/articles/PMC2077933?pdf=render |
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