Lysosomal membrane integrity in fibroblasts derived from patients with Gaucher disease
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...
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| Format: | Article |
| Language: | English |
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Japan Society for Cell Biology
2023-12-01
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| Series: | Cell Structure and Function |
| Subjects: | |
| Online Access: | https://www.jstage.jst.go.jp/article/csf/49/1/49_23066/_html/-char/en |
| _version_ | 1827376452671111168 |
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| author | Asuka Hamamoto Natsuki Kita Siddabasave Gowda B. Gowda Hiroyuki Takatsu Kazuhisa Nakayama Makoto Arita Shu-Ping Hui Hye-Won Shin |
| author_facet | Asuka Hamamoto Natsuki Kita Siddabasave Gowda B. Gowda Hiroyuki Takatsu Kazuhisa Nakayama Makoto Arita Shu-Ping Hui Hye-Won Shin |
| author_sort | Asuka Hamamoto |
| collection | DOAJ |
| description | 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. Key words: glucosylceramide, lysosome, Gaucher disease, lysosomotropic agent |
| first_indexed | 2024-03-08T12:11:11Z |
| format | Article |
| id | doaj.art-dac1dd9dc36f40f89f54c83bb79bee6d |
| institution | Directory Open Access Journal |
| issn | 0386-7196 1347-3700 |
| language | English |
| last_indexed | 2024-03-08T12:11:11Z |
| publishDate | 2023-12-01 |
| publisher | Japan Society for Cell Biology |
| record_format | Article |
| series | Cell Structure and Function |
| spelling | doaj.art-dac1dd9dc36f40f89f54c83bb79bee6d2024-01-22T23:51:53ZengJapan Society for Cell BiologyCell Structure and Function0386-71961347-37002023-12-0149111010.1247/csf.23066csfLysosomal membrane integrity in fibroblasts derived from patients with Gaucher diseaseAsuka Hamamoto0Natsuki Kita1Siddabasave Gowda B. Gowda2Hiroyuki Takatsu3Kazuhisa Nakayama4Makoto Arita5Shu-Ping Hui6Hye-Won Shin7Graduate School of Pharmaceutical Science, Kyoto UniversityGraduate School of Pharmaceutical Science, Kyoto UniversityFaculty of Health Sciences, Hokkaido UniversityGraduate School of Pharmaceutical Science, Kyoto UniversityGraduate School of Pharmaceutical Science, Kyoto UniversityLaboratory for Metabolomics, RIKEN Center of Integrative Medical SciencesFaculty of Health Sciences, Hokkaido UniversityGraduate School of Pharmaceutical Science, Kyoto UniversityGaucher 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. Key words: glucosylceramide, lysosome, Gaucher disease, lysosomotropic agenthttps://www.jstage.jst.go.jp/article/csf/49/1/49_23066/_html/-char/englucosylceramidelysosomegaucher diseaselysosomotropic agent |
| spellingShingle | Asuka Hamamoto Natsuki Kita Siddabasave Gowda B. Gowda Hiroyuki Takatsu Kazuhisa Nakayama Makoto Arita Shu-Ping Hui Hye-Won Shin Lysosomal membrane integrity in fibroblasts derived from patients with Gaucher disease Cell Structure and Function glucosylceramide lysosome gaucher disease lysosomotropic agent |
| title | Lysosomal membrane integrity in fibroblasts derived from patients with Gaucher disease |
| title_full | Lysosomal membrane integrity in fibroblasts derived from patients with Gaucher disease |
| title_fullStr | Lysosomal membrane integrity in fibroblasts derived from patients with Gaucher disease |
| title_full_unstemmed | Lysosomal membrane integrity in fibroblasts derived from patients with Gaucher disease |
| title_short | Lysosomal membrane integrity in fibroblasts derived from patients with Gaucher disease |
| title_sort | lysosomal membrane integrity in fibroblasts derived from patients with gaucher disease |
| topic | glucosylceramide lysosome gaucher disease lysosomotropic agent |
| url | https://www.jstage.jst.go.jp/article/csf/49/1/49_23066/_html/-char/en |
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