Effects of cyclodextrins on GM1-gangliosides in fibroblasts from GM1-gangliosidosis patients
| Autor: | Yoichi Ishitsuka, Yuki Kurauchi, Hiroshi Katsuki, Yuka Horikoshi, Takumi Era, Yuki Maeda, Tetsumi Irie, Yuki Kondo, Toru Takeo, Taishi Higashi, Keiichi Motoyama, Hidetoshi Arima, Naomi Nakagata, Hirokazu Furuya |
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| Rok vydání: | 2015 |
| Předmět: |
Cell Survival
Cell Culture Techniques Phospholipid Ganglioside Storage Diseases Down-Regulation Pharmaceutical Science G(M1) Ganglioside Biology medicine.disease_cause Flow cytometry chemistry.chemical_compound Autophagy Confocal laser scanning microscopy medicine Humans Phospholipids Pharmacology Cyclodextrins Gangliosidosis GM1 Dose-Response Relationship Drug medicine.diagnostic_test Cholesterol GM1 Gangliosidosis Cholera toxin Fibroblasts chemistry Biochemistry lipids (amino acids peptides and proteins) Efflux |
| Zdroj: | Journal of Pharmacy and Pharmacology. 67:1133-1142 |
| ISSN: | 2042-7158 0022-3573 |
| DOI: | 10.1111/jphp.12405 |
| Popis: | Objectives GM1-gangliosidosis is an inherited disorder characterized by the accumulation of GM1-gangliosides in many tissues and organs, particularly in the brain. Currently, there is no treatment available for patients with ganglioside storage diseases. Therefore, we investigated the effects of cyclodextrins (CyDs) on the GM1-ganglioside level in EA1 cells, fibroblasts from patients with GM1-gangliosidosis. Methods The concentrations of cholesterol and phospholipids in supernatants were determined by Cholesterol E-test Wako and Phospholipid C-test Wako, respectively. The effects of CyDs on GM1-ganglioside levels in EA1 cells using fluorescence-labelled cholera toxin B-subunit, which can bind to GM1-gangliosides specifically, were investigated by flow cytometry and confocal laser scanning microscopy. Key findings The treatment with methylated CyDs, hydroxypropylated CyDs and branched CyDs decreased GM1-ganglioside levels in EA1 cells at 1 mm for 24 h. Unexpectedly, there was no significant change in the efflux of cholesterol or phospholipids from the cells after treatment with CyDs under the same experimental conditions, indicating that the efflux of membrane components is not associated with down-regulation of GM1-ganglioside levels in EA1 cells upon CyDs treatment. Conclusions CyDs may have the potential as drugs for GM1-gangliosidosis, although the mechanism should be thereafter clarified. |
| Databáze: | OpenAIRE |
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