| Autor: |
Yushan Wang, Xiaona Zhang, Tao Wang, Wen Liu, Lijing Wang, Ling Hao, Mengwei Ju, Rong Xiao |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Frontiers in Cell and Developmental Biology, Vol 8 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2296-634X |
| DOI: |
10.3389/fcell.2020.580599 |
| Popis: |
Abnormality in cholesterol homeostasis in the brain is a feature of Alzheimer’s disease (AD). 27-Hydroxycholesterol (27-OHC) has been identified as a possible biomarker of AD, but its effects on cholesterol metabolism have not been fully characterized. This study was aimed to investigate the impacts of 27-OHC on cholesterol metabolism in nerve cells. SH-SY5Y cells and C6 cells were co-cultured and treated with 5, 10, and 20 μM 27-OHC for 24 h. Results showed that 27-OHC decreased cholesterol levels and up-regulated the expression of transport-related proteins in C6 cells. In SH-SY5Y cells, 27-OHC increased cholesterol accumulation, especially on plasma membrane (PM), which was consistent with the up-regulation of expressions of cholesterol endocytosis receptors, lipid raft-related proteins, and cholesterol esterase. Simultaneously, accumulation of membrane cholesterol promoted cholesterol conversion to 24S-OHC by CYP46A1(24S-hydroxylase) transfer from the endoplasmic reticulum (ER) to PM. Besides, Aβ levels were elevated in SH-SY5Y cells after 27-OHC treatment. Our results suggest that 27-OHC motivates the transfer of astrocyte-derived cholesterol to neurons. Although there exists a feedback mechanism that excessive cholesterol promotes its conversion to 24S-OHC, the increased cholesterol induced by 27-OHC could not be wholly offset in neurons. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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