期刊
HUMAN MOLECULAR GENETICS
卷 26, 期 22, 页码 4327-4339出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddx319
关键词
-
资金
- Rosetrees Trust
- Glasgow Children's Hospital Charity
- Fight for Sight, Eye Research Fund (Edinburgh and Lothian Health Foundation, ELHF)
- Visual Research Trust
- Fight for Sight [1419/20, URP12] Funding Source: researchfish
- Glasgow Children's Hospital Charity [YRSS/PSG/2014/06] Funding Source: researchfish
- Rosetrees Trust [M160-F1] Funding Source: researchfish
Cholesterol accumulation beneath the retinal pigment epithelium (RPE) cells is supposed to contribute the pathogenesis of age-related macular degeneration (AMD). Cholesterol efflux genes (APOE and ABCA1) were identified as risk factors for AMD, although how cholesterol efflux influences accumulation of this lipid in sub-RPE deposits remains elusive. The 18 kDa translocator protein, TSPO, is a cholesterol-binding protein implicated in mitochondrial cholesterol transport. Here, we investigate the function of TSPO in cholesterol efflux from the RPE cells. We demonstrate in RPE cells that TSPO specific ligands promoted cholesterol efflux to acceptor (apo) lipoprotein and human serum, while loss of TSPO resulted in impaired cholesterol efflux. TSPO-/- RPE cells also had significantly increased production of reactive oxygen species (ROS) and upregulated expression of proinflammatory cytokines (IL-1 beta and TNF alpha). Cholesterol (oxidized LDL) uptake and accumulation were markedly increased in TSPO-/- RPE cells. Finally, in aged RPE cells, TSPO expression was reduced and cholesterol efflux impaired. These findings provide a new pharmacological concept to treat early AMD patients by stimulating cellular cholesterol removal with TSPO specific ligands or by overexpression of TSPO in RPE cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据