Vascular Biology Center, Georgia Health Sciences University, 1459 Laney-Walker Boulevard, CB-3701, Augusta, GA 30912, USA.
Mamm Genome. 2012 Dec;23(11-12):758-63. doi: 10.1007/s00335-012-9419-x. Epub 2012 Sep 4.
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.
中性鞘磷脂酶 2（nSMase2）的上调最近被证明是烟雾吸入和肺部气肿变化之间的分子联系。在这里，我们报告 nSMase2 缺陷会损害小鼠的肺发育。我们之前曾表明，脆性骨病（fro）小鼠的 Smpd3 基因突变，使 nSMase2 失去催化活性。对肺表型的分析表明，fro 小鼠的肺泡异常增大，呼吸系统顺应性增加，与肺气肿的形态和功能表现相似。对 fro 肺部鞘脂含量的分析显示 C14:0 神经酰胺水平降低，但神经鞘氨醇或神经鞘氨醇-1-磷酸水平没有显著变化。总之，我们的数据表明 nSMase2 活性和神经酰胺水平对肺发育和功能至关重要。基于我们的数据，神经酰胺不能再被视为对肺功能有害的脂质。
