Chatelut M, Leruth M, Harzer K, Dagan A, Marchesini S, Gatt S, Salvayre R, Courtoy P, Levade T
INSERM Unit 466, Laboratoire de Biochimie, Maladies Métaboliques, Institut Louis Bugnard, C.H.U. Rangueil, Toulouse, France.
FEBS Lett. 1998 Apr 10;426(1):102-6. doi: 10.1016/s0014-5793(98)00325-1.
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-(14)C]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.
由于据报道，细胞刺激后第二信使神经酰胺的生成发生在内体/溶酶体区室，我们研究了溶酶体中形成的神经酰胺是否能够逃离该区室。在来自对照个体和一名患有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，检测了由低密度脂蛋白相关的[神经酰胺-3H]鞘磷脂或[硬脂酰-1-(14)C]硫脂的溶酶体内水解产生的放射性标记神经酰胺的代谢命运。将这种放射性神经酰胺的行为与源自硫脂降解的荧光（丽丝胺-罗丹明基）神经酰胺类似物的行为进行了比较。在法伯细胞中，天然的放射性标记神经酰胺完全未被降解并积聚在溶酶体中，而荧光衍生物则迅速转化为鞘磷脂。这些发现强烈表明，与荧光衍生物不同，内源性长链神经酰胺无法从溶酶体中排出因此溶酶体神经酰胺不太可能是一种生物调节分子。
