摘要
Lipid metabolism and oxidative stress are major contributors to ocular diseases, including drusen formation and photoreceptor damage. Aster-B, encoded by GRAMD1B, mediates the non-vesicular transport of cholesterol and carotenoids and is highly expressed in the human eye, though its specific ocular functions remain unknown. We investigated Aster-B’s role in ARPE-19 cells, a model of the retinal pigment epithelium (RPE), using CRISPR/dCas9 to generate an Aster-B-expressing cell line. Aster-B expression significantly improved cell survival under oxidative stress induced by hydrogen peroxide (H2O2) and was associated with the activation of the p53 and TGFβ signaling pathways, indicating a role in modulating stress responses. To confirm its lipid transport activity, we treated cholesterol-depleted cells with carotenoids and tracked their localization. In Aster-B-expressing cells, carotenoids accumulated in mitochondria, while in control cells, they remained in other cellular compartments. Under oxidative stress, mitochondrial carotenoid levels declined in Aster-B-expressing cells but not in control cells. Interestingly, carotenoids enhanced survival in control cells exposed to H2O2 but had a detrimental effect in Aster-B-expressing cells, suggesting that carotenoid function is context and location dependent. These findings highlight Aster-B’s role in coordinating lipid transport and stress responses in the RPE, with implications for oxidative stress-related eye diseases.
摘要译文
脂质代谢和氧化应激是眼部疾病的主要因素，包括drusen形成和感光受体损伤。由GRAMD1B编码的Aster-B介导胆固醇和类胡萝卜素的非尿液转运，并且在人眼中高度表达，尽管其特定的眼功能尚不清楚。我们使用CRISPR/DCAS9在ARPE-19细胞（RPE）的ARPE-19细胞中的作用（ARPE-19细胞（RPE）模型）来生成表达Aster-B的细胞系。Aster-B表达在通过氧化氢诱导的氧化应激（H2O2）引起的氧化应激下显着改善了细胞存活，并与p53和TGFβ信号通路的激活相关，表明在调节应力反应中起作用。为了确认其脂质转运活性，我们用类胡萝卜素处理了胆固醇的细胞，并跟踪了它们的定位。在表达Aster-B的细胞中，类胡萝卜素积聚在线粒体中，而在对照细胞中，它们仍留在其他细胞室中。在氧化应激下，线粒体类胡萝卜素水平在表达紫B的细胞中下降，但在对照细胞中却没有下降。有趣的是，类胡萝卜素增强了暴露于H2O2的对照细胞中的生存率，但在表达Aster-B的细胞中具有有害作用，这表明类胡萝卜素功能是上下文和位置依赖性的。这些发现突出了Aster-B在RPE中的脂质转运和应力反应中的作用，这对与氧化应激相关的眼部疾病有影响。
Vidya Gopakumar; Johannes von Lintig. Aster-B Modulates Oxidative Stress Responses and Carotenoid Distribution in ARPE-19 Cells[J]. Antioxidants, 2025,14(5): 575