PHOSPHATIDYLCHOLINE STORAGE IN MUCOLIPIDOSIS-IV
PHOSPHATIDYLCHOLINE STORAGE IN MUCOLIPIDOSIS-IV
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DOI：
10.1016/0009-8981(89)90184-8
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发表时间：
1989-05-15
影响因子：
5
通讯作者：
BACH, G
中科院分区：
文献类型：
--
作者：
BARGAL, R;BACH, G
用亚细胞梯度分离法研究了粘脂沉积症IV型（MLIV）患者培养的成纤维细胞中磷脂酰胆碱（PC）的积累。标记的PC积累在MLIV细胞的次级溶酶体中的速率显着较高时，与正常对照组相比，与前体[32 P]磷酸盐或[14 C]胆碱孵育。脉冲4天后观察到这种蓄积，并在7天追踪后变得更加严重，导致MLIV溶酶体部分中该物质比正常对照增加30倍。另一方面，在受影响细胞的漂浮部分中，放射性PC没有显著增加，同样，MLIV和对照组中标记PC从该部分中消失的速率相同。在MLIV的溶酶体中PC的保留也可以证明培养的成纤维细胞与放射性磷脂本身孵育后。在这些实验中，在内体中也观察到MLIV中标记的PC增加，内体参与了PC进入溶酶体的摄取过程。导致MLIV中这种储存的代谢缺陷尚未确定，但这些数据表明MLIV中磷脂的溶酶体catalysis受损。
The accumulation of phosphatidylcholine (PC) incultured fibroblasts of mucolipidosis IV (MLIV) patients was studied by subcellular fractionation on percoll gradients. Labelled PC accumulated in secondary lysosomes of the MLIV cells in significantly higher rates when compared to normal controls incubated with the precursors [32P]phosphate or [14C]choline. This accumulation was noted after 4 days of pulse and became more profound after 7 days of chase resulting in a 30-fold increse of this substance in the lysosomal fraction of MLIV compared to normal controls. On the other hand, no significant increase of radioactive PC was demonstrated in the buoyant fraction of the affected cells, and similarly the rate of disappearance of labeled PC from this fraction was identical in MLIV and controls. The retention of PC in lysosomes of MLIV could also be demonstrated following incubation of cultured fibroblasts with the radioactive phospholipid itself. In these experiments increased labelled PC in MLIV was also noted in endosomes, which are involved in the uptake process of PC enroute to the lysosomes. The metabolic defect leading to this storage in MLIV has not yet been identified, but these data indicate impairment in the lysosomal catabolism of phospholipids in MLIV.