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首页> 外文期刊>Molecular genetics and metabolism >Glucosylceramide accumulation is not confined to the lysosome in fibroblasts from patients with Gaucher disease.
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Glucosylceramide accumulation is not confined to the lysosome in fibroblasts from patients with Gaucher disease.

机译：葡萄糖神经酰胺的积累不限于来自高雪氏病患者的成纤维细胞中的溶酶体。

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摘要

Gaucher disease (GD) is an inborn error of glycosphingolipid metabolism resulting from a deficiency of the lysosomal enzyme beta-glucosidase leading to the accumulation of glucosylceramide (GC) in lysosomes of affected cells. In order to determine the effect of GC accumulation on intracellular lipid content in fibroblasts from patients with GD, we measured individual species of ceramide, di- and trihexosylceramide, sphingomyelin, phosphatidylcholine, phosphatidylinositol and phosphatidylglycerol using electrospray ionisation-tandem mass spectrometry. The different subspecies of each lipid class correlated with each other and were summed to give total lipid concentrations. In addition to GC, we also noted secondary elevations in other lipids, especially in type 2 GD. Sub-cellular fractionation showed that GC was not confined to the lysosome but increased throughout the cell. The sequelae of extra-lysosomal accumulation may have implications in the pathogenic mechanisms of GD by interaction with biochemical and metabolic pathways located outside the lysosome. The elevation of ceramide in confluent type 2 GD fibroblasts redistributed from its primary site of accumulation in the lysosome to the endosomal region at four-weeks post-confluence. The accumulation of lipids in the endosome and lysosome suggests both impaired trafficking of lipids and reduced capacity of the lysosome to degrade lipids.
机译：高雪氏病（GD）是糖鞘脂代谢的先天性错误，是由于溶酶体酶β-葡糖苷酶的缺乏导致糖苷神经酰胺（GC）在受影响细胞的溶酶体中积聚。为了确定GC积累对GD患者成纤维细胞中细胞内脂质含量的影响，我们使用电喷雾电离串联质谱法测量了神经酰胺，二和三己糖基神经酰胺，鞘磷脂，磷脂酰胆碱，磷脂酰肌醇和磷脂酰甘油的各个物种。每个脂质类别的不同亚种彼此相关，并相加得出总脂质浓度。除GC外，我们还注意到其他脂质的继发升高，尤其是2型GD。亚细胞分级分离表明，GC不仅限于溶酶体，而且在整个细胞中均增加。溶酶体外积累的后遗症可能通过与溶酶体外部的生化和代谢途径相互作用而影响GD的致病机制。汇合后四周，汇合的2型GD成纤维细胞中神经酰胺的升高从其在溶酶体中积累的主要部位重新分布到了内体区域。脂质体在内体和溶酶体中的积累表明脂质的运输受损和溶酶体降解脂质的能力降低。

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