Natural ceramide is unable to escape the lysosome, in contrast to a fluorescent analogue

FEBS Letters

Marchesini, Sergio⁴  Leruth, Michèle²  Gatt, Shimon³  Dagan, Arie³  Salvayre, Robert⁵  Harzer, Klaus¹  Levade, Thierry⁵  Chatelut, Martine⁵  Courtoy, Pierre² 

[1] Laboratory of Neurochemistry, Institut für Hirnforschung, Tübingen, Germany;Cell Biology Unit, ICP, Université Catholique de Louvain, Brussels, Belgium;Department of Biochemistry, Hebrew University-Hadassah School of Medicine, Jerusalem, Israel;Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy;INSERM Unit 466, Laboratoire de Biochimie, Maladies Métaboliques, Institut Louis Bugnard, Bât. L3, C.H.U. Rangueil, 1 Avenue Jean Poulhès, F-31403 Toulouse Cedex 4, France

关键词: Ceramide;    Lysosome;    Farber disease;    Sphingomyelin;    Sulfatide;    SM;    sphingomyelin;    LR12-CS;    N-lissamine-rhodaminyl-(12-aminododecanoyl)-cerebroside 3-sulfate (or sulfatide);    TLC;    thin layer chromatography;    FCS;    fetal calf serum;    LDL;    low density lipoprotein;   

DOI  :  10.1016/S0014-5793(98)00325-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Since the generation upon cell stimulation of the second messenger ceramide has been reported to occur in an endosomal/lysosomal compartment, we investigated whether ceramide formed in the lysosomes can escape this compartment. The metabolic fate of radiolabelled ceramide produced by intralysosomal hydrolysis of LDL-associated [ceramide-³H]sphingomyelin or [stearoyl-1-¹⁴C]sulfatide was examined in fibroblasts from control individuals and a patient with inborn lysosomal ceramidase deficiency (Farber disease). The behavior of this radioactive ceramide was compared to that of a fluorescent (lissamine-rhodaminyl) ceramide analogue deriving from sulfatide degradation. While in Farber cells the natural, radiolabelled ceramide remained completely undegraded and accumulated in the lysosomes, the fluorescent derivative was rapidly converted to sphingomyelin. These findings strongly suggest that, in contrast to fluorescent derivatives, endogenous long-chain ceramide is unable to exit from lysosomes, therefore making the lysosomal ceramide unlikely to be a biomodulatory molecule.

【 授权许可】

Unknown