| Autor: |
Chao Xue, Peng Zeng, Ke Gong, Qian Li, Zian Feng, Mengyao Wang, Shasha Chen, Yanfang Yang, Jiaqi Li, Shuang Zhang, Zequn Yin, Yingquan Liang, Tengteng Yan, Miao Yu, Ke Feng, Dan Zhao, Xiaoxiao Yang, Xia Zhang, Likun Ma, Yasuko Iwakiri, Liang Chen, Xiaoqiang Tang, Yuanli Chen, Houzao Chen, Yajun Duan |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 43, Iss 9, Pp 114691- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2024.114691 |
| Popis: |
Summary: The strategy of lowering cholesterol levels by promoting cholesterol excretion is still lacking, and few molecular targets act on multiple cholesterol metabolic processes. In this study, we find that Nogo-B deficiency/inhibition simultaneously promotes hepatic uptake of cholesterol and cholesterol excretion. Nogo-B deficiency decreases cholesterol levels by activating ATP-binding cassette transporters (ABCs), apolipoprotein E (ApoE), and low-density lipoprotein receptor (LDLR) expression. We discover that Nogo-B interacts with liver X receptor α (LXRα), and Nogo-B deficiency inhibits ubiquitination degradation of LXRα, thereby enhancing its function on cholesterol excretion. Decreased cellular cholesterol levels further activate SREBP2 and LDLR expression, thereby promoting hepatic uptake of cholesterol. Nogo-B inhibition decreases atherosclerotic plaques and cholesterol levels in mice, and Nogo-B levels are correlated to cholesterol levels in human plasma. In this study, Nogo-B deficiency/inhibition not only promotes hepatic uptake of blood cholesterol but also facilitates cholesterol excretion. This study reports a strategy to lower cholesterol levels by inhibiting Nogo-B expression to promote hepatic cholesterol uptake and cholesterol excretion. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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