التفاصيل البيبلوغرافية
| العنوان: |
Differential Effects of 2-Hydroxypropyl-Cyclodextrins on Lipid Accumulation in Npc1-Null Cells |
| المؤلفون: |
Sanzana Hoque, Yuki Kondo, Nodoka Sakata, Yusei Yamada, Madoka Fukaura, Taishi Higashi, Keiichi Motoyama, Hidetoshi Arima, Katsumi Higaki, Akio Hayashi, Takaki Komiya, Yoichi Ishitsuka, Tetsumi Irie |
| المصدر: |
International Journal of Molecular Sciences; Volume 21; Issue 3; Pages: 898 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2020 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
Niemann–Pick disease type C, cyclodextrin, 2-hydroxypropyl-β-cyclodextrin, 2-hydroxypropyl-γ-cyclodextrin, miglustat, cholesterol, lysosome, sphingolipid, sphingomyelin |
| جغرافية الموضوع: |
agris |
| الوصف: |
Niemann–Pick disease type C (NPC) is an autosomal recessive disorder characterized by abnormal accumulation of free cholesterol and sphingolipids in lysosomes. The iminosugar miglustat, which inhibits hexosylceramide synthesis, is used for NPC treatment, and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), a cyclic oligosaccharide derivative, is being developed to treat NPC. Moreover, therapeutic potential of 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CD) was shown in NPC models, although its mechanism of action remains unclear. Here, we investigated the effects of HP-β-CD, HP-γ-CD, and their homolog 2-hydroxypropyl-α-cyclodextrin (HP-α-CD) on lipid accumulation in Npc1-null Chinese hamster ovary (CHO) cells compared with those of miglustat. HP-β-CD and HP-γ-CD, unlike HP-α-CD, reduced intracellular free cholesterol levels and normalized the lysosome changes in Npc1-null cells but not in wild-type CHO cells. In contrast, miglustat did not normalize intracellular free cholesterol accumulation or lysosome changes in Npc1-null cells. However, miglustat decreased the levels of hexosylceramide and tended to increase those of sphingomyelins in line with its action as a glucosylceramide synthase inhibitor in both Npc1-null and wild-type CHO cells. Interestingly, HP-β-CD and HP-γ-CD, unlike HP-α-CD, reduced sphingomyelins in Npc1-null, but not wild-type, cells. In conclusion, HP-β-CD and HP-γ-CD reduce the accumulation of sphingolipids, mainly sphingomyelins, and free cholesterol as well as lysosome changes in Npc1-null, but not in wild-type, CHO cells. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
Molecular Neurobiology; https://dx.doi.org/10.3390/ijms21030898 |
| DOI: |
10.3390/ijms21030898 |
| الاتاحة: |
https://doi.org/10.3390/ijms21030898 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: |
edsbas.B84AFDB2 |
| قاعدة البيانات: |
BASE |