Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease in mice (Nature Medicine, 11:491-498, May 2005)

報告日期: 2005/10/11
報告時間: 15:10/16:00
報告學生: 萬書彣 (英)
講評老師: 謝奇璋
附件下載:

Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease in mice

 

Speaker: 萬書彣

Commentator: 謝奇璋 老師

Time: 15:10-16:00 10/11/2005

Place: Room 602

 

Abstract

The pathogenesis of pulmonary emphysema is characterized by the apoptosis of alveolar cells. Ceramide is a second messenger lipid and is involved in the apoptosis1, oxidative stress1 and proteolysis2 in endothelial cells. The VEGF receptor inhibitor SU5416 induced alveolar cell apoptosis and ceramide synthesis by de novo pathway as the major mechanism in both rats and mice. VEGFR blockade-induced emphysema was attenuated by inhibition of de novo ceramide synthesis. Exogenous administration of short-chain ceramide (C12 ceramide) induced alveolar cells and endothelial cells apoptosis. Excessive ceramide triggered self-amplification of ceramide synthesis through sphingomyelin breakdown. In clinical study, cigarette smoking is the risk factor for the pulmonary emphysema3. In this study, the level of ceramide increased in lung endothelial cells by cigarette smoke stimulation. From clinical emphysematous sample, cigarette  smoke not only increased the absolute levels of ceramide, but also influenced the patterns of ceramide species expression. The linkage of ceramide and emphysema may provide a potential target to slow the alveolar damage in the chronic lung disease.

 

References:

1.     Hannun, Y. A. and Obeid, L. M. (2002). The ceramide-centric universe of lipid-mediated cell regulation: stress encounters of the lipid kind. J. Biol. Chem. 277, 25847-25850.

2.     Reunanen, N., et al. (1998). Enhancement of fibroblast collagenase (matrix metalloproteinase-1) gene expression by ceramide is mediated by extracellular signal-regulated and stress-activated protein kinase pathway. J. Biol. Chem. 273, 5137-5145.

3.     Petrache, I., et al. (2005). Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease in mice. Nat. Med. 11, 491-498.