Lysosomal membrane integrity in fibroblasts derived from patients with Gaucher disease

IF 2 4区 生物学 Q4 CELL BIOLOGY
Asuka Hamamoto, Natsuki Kita, Siddabasave Gowda B Gowda, Hiroyuki Takatsu, Kazuhisa Nakayama, Makoto Arita, Shu-Ping Hui, Hye-Won Shin
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引用次数: 0

Abstract

Gaucher disease (GD) is a recessively inherited lysosomal storage disorder characterized by a deficiency of lysosomal glucocerebrosidase (GBA1). This deficiency results in the accumulation of its substrate, glucosylceramide (GlcCer), within lysosomes. Here, we investigated lysosomal abnormalities in fibroblasts derived from patients with GD. It is noteworthy that the cellular distribution of lysosomes and lysosomal proteolytic activity remained largely unaffected in GD fibroblasts. However, we found that lysosomal membranes of GD fibroblasts were susceptible to damage when exposed to a lysosomotropic agent. Moreover, the susceptibility of lysosomal membranes to a lysosomotropic agent could be partly restored by exogenous expression of wild-type GBA1. Here, we report that the lysosomal membrane integrity is altered in GD fibroblasts, but lysosomal distribution and proteolytic activity is not significantly altered.

戈谢病患者成纤维细胞溶酶体膜的完整性
戈谢病(GD)是一种隐性遗传的溶酶体储积症,其特征是溶酶体葡萄糖脑苷脂酶(GBA1)缺乏。这种缺乏症会导致其底物葡萄糖醛酸(GlcCer)在溶酶体内蓄积。在这里,我们研究了来自 GD 患者的成纤维细胞的溶酶体异常。值得注意的是,在 GD 成纤维细胞中,溶酶体的细胞分布和溶酶体蛋白水解活性基本未受影响。然而,我们发现,当暴露于溶酶体促进剂时,GD 成纤维细胞的溶酶体膜很容易受到损伤。此外,溶酶体膜对溶酶体促进剂的易感性可通过外源表达野生型 GBA1 得到部分恢复。在这里,我们报告了广东成纤维细胞溶酶体膜完整性的改变,但溶酶体分布和蛋白水解活性并没有显著改变。
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来源期刊
Cell structure and function
Cell structure and function 生物-细胞生物学
CiteScore
2.50
自引率
0.00%
发文量
6
审稿时长
>12 weeks
期刊介绍: Cell Structure and Function is a fully peer-reviewed, fully Open Access journal. As the official English-language journal of the Japan Society for Cell Biology, it is published continuously online and biannually in print. Cell Structure and Function publishes important, original contributions in all areas of molecular and cell biology. The journal welcomes the submission of manuscripts on research areas such as the cell nucleus, chromosomes, and gene expression; the cytoskeleton and cell motility; cell adhesion and the extracellular matrix; cell growth, differentiation and death; signal transduction; the protein life cycle; membrane traffic; and organelles.
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