Ceramide synthases expression and role of ceramide synthase-2 in the lung: insight from human lung cells and mouse models.
Increases in ceramide levels have been implicated in the pathogenesis of both acute or chronic lung injury models. However, the role of individual ceramide species, or of the enzymes that are responsible for their synthesis, in lung health and disease has not been clarified. We now show that C24- an...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3653891?pdf=render |
| _version_ | 1818499789211303936 |
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| author | Irina Petrache Krzysztof Kamocki Christophe Poirier Yael Pewzner-Jung Elad L Laviad Kelly S Schweitzer Mary Van Demark Matthew J Justice Walter C Hubbard Anthony H Futerman |
| author_facet | Irina Petrache Krzysztof Kamocki Christophe Poirier Yael Pewzner-Jung Elad L Laviad Kelly S Schweitzer Mary Van Demark Matthew J Justice Walter C Hubbard Anthony H Futerman |
| author_sort | Irina Petrache |
| collection | DOAJ |
| description | Increases in ceramide levels have been implicated in the pathogenesis of both acute or chronic lung injury models. However, the role of individual ceramide species, or of the enzymes that are responsible for their synthesis, in lung health and disease has not been clarified. We now show that C24- and C16-ceramides are the most abundant lung ceramide species, paralleled by high expression of their synthetic enzymes, ceramide synthase 2 (CerS2) and CerS5, respectively. Furthermore, the ceramide species synthesis in the lung is homeostatically regulated, since mice lacking very long acyl chain C24-ceramides due to genetic deficiency of CerS2 displayed a ten-fold increase in C16-ceramides and C16-dihydroceramides along with elevation of acid sphingomyelinase and CerS5 activities. Despite relatively preserved total lung ceramide levels, inhibition of de novo sphingolipid synthesis at the level of CerS2 was associated with significant airflow obstruction, airway inflammation, and increased lung volumes. Our results suggest that ceramide species homeostasis is crucial for lung health and that CerS2 dysfunction may predispose to inflammatory airway and airspace diseases. |
| first_indexed | 2024-12-10T20:34:22Z |
| format | Article |
| id | doaj.art-34e170a9c540460bb459a106214234dc |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T20:34:22Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-34e170a9c540460bb459a106214234dc2022-12-22T01:34:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6296810.1371/journal.pone.0062968Ceramide synthases expression and role of ceramide synthase-2 in the lung: insight from human lung cells and mouse models.Irina PetracheKrzysztof KamockiChristophe PoirierYael Pewzner-JungElad L LaviadKelly S SchweitzerMary Van DemarkMatthew J JusticeWalter C HubbardAnthony H FutermanIncreases in ceramide levels have been implicated in the pathogenesis of both acute or chronic lung injury models. However, the role of individual ceramide species, or of the enzymes that are responsible for their synthesis, in lung health and disease has not been clarified. We now show that C24- and C16-ceramides are the most abundant lung ceramide species, paralleled by high expression of their synthetic enzymes, ceramide synthase 2 (CerS2) and CerS5, respectively. Furthermore, the ceramide species synthesis in the lung is homeostatically regulated, since mice lacking very long acyl chain C24-ceramides due to genetic deficiency of CerS2 displayed a ten-fold increase in C16-ceramides and C16-dihydroceramides along with elevation of acid sphingomyelinase and CerS5 activities. Despite relatively preserved total lung ceramide levels, inhibition of de novo sphingolipid synthesis at the level of CerS2 was associated with significant airflow obstruction, airway inflammation, and increased lung volumes. Our results suggest that ceramide species homeostasis is crucial for lung health and that CerS2 dysfunction may predispose to inflammatory airway and airspace diseases.http://europepmc.org/articles/PMC3653891?pdf=render |
| spellingShingle | Irina Petrache Krzysztof Kamocki Christophe Poirier Yael Pewzner-Jung Elad L Laviad Kelly S Schweitzer Mary Van Demark Matthew J Justice Walter C Hubbard Anthony H Futerman Ceramide synthases expression and role of ceramide synthase-2 in the lung: insight from human lung cells and mouse models. PLoS ONE |
| title | Ceramide synthases expression and role of ceramide synthase-2 in the lung: insight from human lung cells and mouse models. |
| title_full | Ceramide synthases expression and role of ceramide synthase-2 in the lung: insight from human lung cells and mouse models. |
| title_fullStr | Ceramide synthases expression and role of ceramide synthase-2 in the lung: insight from human lung cells and mouse models. |
| title_full_unstemmed | Ceramide synthases expression and role of ceramide synthase-2 in the lung: insight from human lung cells and mouse models. |
| title_short | Ceramide synthases expression and role of ceramide synthase-2 in the lung: insight from human lung cells and mouse models. |
| title_sort | ceramide synthases expression and role of ceramide synthase 2 in the lung insight from human lung cells and mouse models |
| url | http://europepmc.org/articles/PMC3653891?pdf=render |
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