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FoxO1在氧化应激诱导的颗粒细胞凋亡中的关键作用及葡萄籽原花青素B2的保护作用

Critical Role of FoxO1 in Granulosa Cell Apoptosis Caused by Oxidative Stress and Protective Effects of Grape Seed Procyanidin B2.

作者信息

Zhang Jia-Qing, Gao Bin-Wen, Wang Jing, Ren Qiao-Ling, Chen Jun-Feng, Ma Qiang, Zhang Zi-Jing, Xing Bao-Song

机构信息

Institute of Animal Husbandry and Veterinary Science, Henan Academy of Agricultural Sciences, Zhengzhou 450008, China.

出版信息

Oxid Med Cell Longev. 2016;2016:6147345. doi: 10.1155/2016/6147345. Epub 2016 Jan 19.

DOI:10.1155/2016/6147345
PMID:27057282
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4745910/
Abstract

Reactive oxygen species (ROS) are closely related to the follicular granulosa cell apoptosis. Grape seed procyanidin B2 (GSPB2) has been reported to possess potent antioxidant activity. However, the GSPB2-mediated protective effects and the underlying molecular mechanisms in granulosa cell apoptosis process remain unknown. In this study, we showed for the first time that GSPB2 treatment decreased FoxO1 protein level, improved granulosa cell viability, upregulated LC3-II protein level, and reduced granulosa cell apoptosis rate. Under a condition of oxidative stress, GSPB2 reversed FoxO1 nuclear localization and increased its level in cytoplasm. In addition, FoxO1 knockdown inhibited the protective effects of GSPB2 induced. Our findings suggest that FoxO1 plays a pivotal role in regulating autophagy in granulosa cells, GSPB2 exerts a potent and beneficial role in reducing granulosa cell apoptosis and inducing autophagy process, and targeting FoxO1 could be significant in fighting against oxidative stress-reduced female reproductive system diseases.

摘要

活性氧(ROS)与卵泡颗粒细胞凋亡密切相关。据报道,葡萄籽原花青素B2(GSPB2)具有强大的抗氧化活性。然而,GSPB2介导的颗粒细胞凋亡过程中的保护作用及潜在分子机制仍不清楚。在本研究中,我们首次表明,GSPB2处理降低了FoxO1蛋白水平,提高了颗粒细胞活力,上调了LC3-II蛋白水平,并降低了颗粒细胞凋亡率。在氧化应激条件下,GSPB2逆转了FoxO1的核定位并增加了其在细胞质中的水平。此外,敲低FoxO1可抑制GSPB2诱导的保护作用。我们的研究结果表明,FoxO1在调节颗粒细胞自噬中起关键作用,GSPB2在减少颗粒细胞凋亡和诱导自噬过程中发挥强大而有益的作用,靶向FoxO1在对抗氧化应激导致的女性生殖系统疾病中可能具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b35/4745910/3bf145b274e8/OMCL2016-6147345.009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b35/4745910/75ab29b6b9b1/OMCL2016-6147345.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b35/4745910/c1d875243667/OMCL2016-6147345.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b35/4745910/b65bca968127/OMCL2016-6147345.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b35/4745910/8373c233bd5f/OMCL2016-6147345.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b35/4745910/481f60085c50/OMCL2016-6147345.007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b35/4745910/3bf145b274e8/OMCL2016-6147345.009.jpg

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