摘要
Impairment of retinal pigment epithelial (RPE) cells is considered a key contributor to the development of age-related macular degeneration. Apoptosis-related protein 3 (APR3) was recently discovered after treatment with all-trans retinoic acid, a pivotal molecule in RPE cells. However, the function of APR3 remains poorly understood. In the present study, we found that APR3 could interact with nuclear factor (erythroid-derived 2)-like 2, which is a regulator of phase II enzymes, and that knockdown of APR3 promoted nuclear factor (erythroid-derived 2)-like 2 nuclear translocation and activated expression of phase II enzymes, which was accompanied by improved redox status and mitochondrial activity. Overexpression of APR3 revealed its mitochondrial localization and induced a robust production of reactive oxygen species that was accompanied by impaired mitochondrial oxygen consump tion, complex activity, and lower ATP content, resulting in significant changes in mitochondrial structure, which may contribute to cell apoptosis. High doses of all-trans retinoic acid treatment were found to significantly induce APR3 expression, increase reactive oxygen species levels, and decrease ATP content, which were abolished by knockdown of APR3. These results indicate that APR3 plays a vital role in regulating redox status and mitochondrial activity and thus suggest APR3 might be a potential novel target for study of treatment of age-related macular degeneration.—Li, Y., Zou, X., Gao, J., Cao, K., Feng, Z., Liu, J. APR3 modulates oxidative stress and mitochondrial function in ARPE-19 cells. FASEB J. 32, 5851–5861 (2018). www.fasebj.org
摘要译文
视网膜色素上皮（RPE）细胞的损伤被认为是年龄相关黄斑变性的发展的关键因素。最近用全反式视黄酸处理后，最近发现了凋亡相关的蛋白3（APR3），RPE细胞中的枢轴分子。然而，APR3的职能仍然明白很差。在本研究中，我们发现APR3可以与核因子（红细胞衍生的2）-like 2相互作用，这是II期酶的调节剂，并且4月份促进核因子（红细胞衍生的2）-like 2核转位和激活的相二酶表达，其伴有改善的氧化还原状态和线粒体活性。 APR3的过度表达揭示了其线粒体定位，并诱导了伴随着线粒体氧团块，复杂活性和较低的ATP含量伴随的反应性氧物质的稳健生产，导致线粒体结构的显着变化，这可能有助于细胞凋亡。发现高剂量的全反式视黄酸处理可显着诱导APR3表达，增加反应性氧物质水平，并降低APR3的敲低取消的ATP含量。这些结果表明，APR3在调节氧化还原状态和线粒体活动方面发挥着至关重要的作用，因此表明APR3可能是研究年龄相关黄斑变性治疗的潜在新靶标。 - 李，Y.，Zou，X.，GAO， J.，Cao，K.，Feng，Z.，Liu，J.PR3调节ARPE-19细胞中的氧化应激和线粒体功能。 FASEB J. 32,5851-5861（2018）。 www.fasebj.org.
Yuan Li[1];Xuan Zou[2];Jing Gao[1];Ke Cao[1];Zhihui Feng[1];Jiankang Liu[1]. APR3 modulates oxidative stress and mitochondrial function in ARPE‐19 cells[J]. FASEB Journal, 2018,32(11): 5851-5861