文章基本信息
- 标题：LASS5 is the predominant ceramide synthase isoform involved in de novo sphingolipid synthesis in lung epithelia
- 本地全文：下载
- 作者：Xu, Zhiwei ; Zhou, Jiming ; McCoy, Diann M. 等
- 期刊名称：JLR Papers In Press
- 印刷版ISSN：0022-2275
- 电子版ISSN：1539-7262
- 出版年度：2005
- 卷号：46
- 期号：06
- 页码：1229-1238
- DOI：10.1194/jlr.M500001-JLR200
- 出版社：American Society for Biochemistry and Molecular Biology
- 摘要：Ceramide is a key bioactive mediator that inhibits surfactant phosphatidylcholine (PtdCho) synthesis in lung epithelia. Ceramide availability is governed by sphingomyelin (SM) hydrolysis, but less is known regarding its de novo synthesis. In this study, we observed that ceramide synthesis within murine lung epithelia was associated with high-level ceramide synthase (dihydroceramide synthase) activity. Longevity assurance homolog 5 (LASS5) was the predominant ceramide synthase isoform detected in lung epithelia, whereas relatively lower level expression was detected for the other five mammalian homologs. Pulmonary LASS5 was developmentally regulated, but its expression was spatially and gender nonspecific. Exogenously expressed LASS5 in lung epithelia was membrane-associated, triggering increased ceramide synthesis, whereas knockdown studies using fumonisin B1 or LASS5 small, interfering RNA reduced ceramide synthase activity by 78% or 45%, respectively. Overexpression of LASS5 also reduced PtdCho synthesis, but maximal inhibition was achieved when LASS5 was coexpressed with a plasmid encoding a neutral sphingomyelinase involved in SM hydrolysis.
These results demonstrate that LASS5 is the major ceramide synthase gene product involved in sphingolipid production that may also regulate PtdCho metabolism in pulmonary epithelia.
Abbreviations: CCT, CTP:phosphocholine cytidylyltransferase; FB1, fumonisin B1; LASS1, longevity assurance homolog 1; PtdCho, phosphatidylcholine; siRNA, small interfering RNA; SM, sphingomyelin; SMase, sphingomyelinase; SPT, serine palmitoyltransferase; TNF-
, tumor necrosis factor-
Supplementary key words longevity assurance homolog 5 • dihydroceramide synthase • phosphatidylcholine
扫一扫关注微信
国家哲学社会科学文献中心版权所有