Neutral sphingomyelinase 2 deficiency is associated with lung anomalies similar to emphysema

Christophe Poirier, Evgeny V. Berdyshev, Christiana Dimitropoulou, Natalia V. Bogatcheva, Paul Williams Biddinger, Alexander Dmitriyevich Verin

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Neutral sphingomyelinase 2 (nSMase2) upregulation was recently demonstrated to serve as a molecular link between smoke inhalation and emphysematous changes in lungs. Here we report that nSMase2 deficit impairs lung development in mice. We have shown previously that fragilitas ossium (fro) mice carry a mutation in the Smpd3 gene, rendering nSMase2 catalytically inactive. Analysis of lung phenotype revealed that fro mice have abnormally enlarged alveoli and increased compliance of the respiratory system, similar to morphological and functional manifestations of emphysema. Analysis of sphingolipid content in fro lungs revealed a decreased level of C14:0 ceramide but no significant alterations in the levels of sphingosine or sphingosine-1-phosphate. Altogether, our data suggest that nSMase2 activity and ceramide level are critical for lung development and function. Based on our data, ceramide can no longer be viewed as a lipid solely detrimental to lung function.

Original languageEnglish (US)
Pages (from-to)758-763
Number of pages6
JournalMammalian Genome
Volume23
Issue number11-12
DOIs
StatePublished - Dec 1 2012

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Type A Niemann-Pick Disease
Emphysema
Sphingomyelin Phosphodiesterase
Osteogenesis Imperfecta
Lung
Ceramides
Sphingolipids
Sphingosine
Smoke
Respiratory System
Inhalation
Compliance
Up-Regulation
Phenotype
Lipids
Mutation

ASJC Scopus subject areas

  • Genetics

Cite this

Neutral sphingomyelinase 2 deficiency is associated with lung anomalies similar to emphysema. / Poirier, Christophe; Berdyshev, Evgeny V.; Dimitropoulou, Christiana; Bogatcheva, Natalia V.; Biddinger, Paul Williams; Verin, Alexander Dmitriyevich.

In: Mammalian Genome, Vol. 23, No. 11-12, 01.12.2012, p. 758-763.

Research output: Contribution to journalArticle

Poirier, Christophe ; Berdyshev, Evgeny V. ; Dimitropoulou, Christiana ; Bogatcheva, Natalia V. ; Biddinger, Paul Williams ; Verin, Alexander Dmitriyevich. / Neutral sphingomyelinase 2 deficiency is associated with lung anomalies similar to emphysema. In: Mammalian Genome. 2012 ; Vol. 23, No. 11-12. pp. 758-763.
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