首页    期刊浏览 2025年07月06日 星期日
登录注册

文章基本信息

  • 标题:Metabolism of the unnatural anticancer lipid safingol, l-threo-dihydrosphingosine, in cultured cells
  • 本地全文:下载
  • 作者:Mihaela Dragusin ; Cristian Gurgui ; Günter Schwarzmann
  • 期刊名称:JLR Papers In Press
  • 印刷版ISSN:0022-2275
  • 电子版ISSN:1539-7262
  • 出版年度:2003
  • 卷号:44
  • 期号:9
  • 页码:1772-1779
  • DOI:10.1194/jlr.M300160-JLR200
  • 语种:English
  • 出版社:American Society for Biochemistry and Molecular Biology
  • 摘要:We studied the metabolism of radioactively labeled safingol ( l - threo- dihydrosphingosine) in primary cultured neurons, B104 neuroblastoma cells, and Swiss 3T3 fibroblasts, and compared it to that of its natural stereoisomer d - erythro -dihydrosphingosine. Both sphingoid bases are used as biosynthetic precursors for complex sphingolipids, albeit to different rates. Whereas a considerable amount of the natural sphingoid base is also directed to the catabolic pathway (20–66%, cell type dependent), only a minor amount of the nonnatural safingol is subjected to catabolic cleavage, most of it being N -acylated to the respective stereochemical variant of dihydroceramide. Interestingly, N -acylation of safingol to l - threo -dihydroceramide is less sensitive to fumonisin B1 than the formation of the natural d - erythro -dihydroceramide. In addition, safingol-derived l - threo- dihydroceramide, unlike its physiologic counterpart, is not desaturated. Most of it either accumulates in the cells (up to 50%) or is used as a biosynthetic precursor of the respective dihydrosphingomyelin (up to 45%). About 5% is, however, glucosylated and channeled into the glycosphingolipid biosynthetic pathway. Our results demonstrate that, despite its nonnatural stereochemistry, safingol is recognized and metabolized preferentially by enzymes of the sphingolipid biosynthetic pathway. Furthermore, our data suggest that the cytotoxic potential of safingol is reduced rather than enhanced via its metabolic conversion.
国家哲学社会科学文献中心版权所有