Natural ceramide is unable to escape the lysosome, in contrast to a fluorescent analogue
Natural ceramide is unable to escape the lysosome, in contrast to a fluorescent analogue
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DOI：
10.1016/s0014-5793(98)00325-1
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发表时间：
1998-04-10
期刊：
影响因子：
3.5
通讯作者：
Levade, T
中科院分区：
文献类型：
--
作者：
Chatelut, M;Leruth, M;Levade, T
由于细胞刺激后产生的第二信使神经酰胺已被报道发生在内体/溶酶体室中，我们研究了在溶酶体中形成的神经酰胺是否可以逃离这个室。在对照个体和先天性溶酶体神经酰胺酶缺乏症（法伯病）患者的成纤维细胞中检查了LDL相关[神经酰胺-H-3]鞘磷脂或[硬脂酰-1-C-14]硫苷脂的溶酶体内水解产生的放射性标记神经酰胺的代谢结局。将该放射性神经酰胺的行为与硫苷脂降解产生的荧光（丽沙明-罗丹明基）神经酰胺类似物的行为进行了比较。虽然在法伯细胞中，天然的放射性标记的神经酰胺保持完全未降解并在溶酶体中积累，但荧光衍生物迅速转化为鞘磷脂。这些发现强烈表明，与荧光衍生物相反，内源性长链神经酰胺不能从溶酶体中退出，因此使得溶酶体神经酰胺不太可能是生物调节分子。(C)1998年欧洲生物化学学会联合会。
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-H-3]sphingomyelin or [stearoyl-1-C-14]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. (C) 1998 Federation of European Biochemical Societies.