Ceramide Synthases Expression and Role of Ceramide Synthase-2 in the Lung

Insight from Human Lung Cells and Mouse Models

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

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere62968
JournalPLoS One
Volume8
Issue number5
DOIs
StatePublished - May 14 2013

Fingerprint

ceramides
Ceramides
animal models
lungs
Lung
cells
Health
synthesis
Sphingomyelin Phosphodiesterase
Sphingolipids
Acute Lung Injury
Lung Injury
Airway Obstruction
Enzymes
sphingosine N-acyltransferase
dihydroceramide desaturase
sphingolipids
Lung Diseases
Pneumonia
Homeostasis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Petrache, I., Kamocki, K., Poirier, C., Pewzner-Jung, Y., Laviad, E. L., Schweitzer, K. S., ... Futerman, A. H. (2013). Ceramide Synthases Expression and Role of Ceramide Synthase-2 in the Lung: Insight from Human Lung Cells and Mouse Models. PLoS One, 8(5), [e62968]. https://doi.org/10.1371/journal.pone.0062968

Ceramide Synthases Expression and Role of Ceramide Synthase-2 in the Lung : Insight from Human Lung Cells and Mouse Models. / Petrache, Irina; Kamocki, Krzysztof; Poirier, Christophe; Pewzner-Jung, Yael; Laviad, Elad L.; Schweitzer, Kelly S.; Van Demark, Mary; Justice, Matthew J.; Hubbard, Walter C.; Futerman, Anthony H.

In: PLoS One, Vol. 8, No. 5, e62968, 14.05.2013.

Research output: Contribution to journalArticle

Petrache, I, Kamocki, K, Poirier, C, Pewzner-Jung, Y, Laviad, EL, Schweitzer, KS, Van Demark, M, Justice, MJ, Hubbard, WC & Futerman, AH 2013, 'Ceramide Synthases Expression and Role of Ceramide Synthase-2 in the Lung: Insight from Human Lung Cells and Mouse Models', PLoS One, vol. 8, no. 5, e62968. https://doi.org/10.1371/journal.pone.0062968
Petrache, Irina ; Kamocki, Krzysztof ; Poirier, Christophe ; Pewzner-Jung, Yael ; Laviad, Elad L. ; Schweitzer, Kelly S. ; Van Demark, Mary ; Justice, Matthew J. ; Hubbard, Walter C. ; Futerman, Anthony H. / Ceramide Synthases Expression and Role of Ceramide Synthase-2 in the Lung : Insight from Human Lung Cells and Mouse Models. In: PLoS One. 2013 ; Vol. 8, No. 5.
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