OONO-/MMP2/MMP9 pathway-mediated apoptosis of porcine granulosa cells is associated with DNA damage

文献类型： 外文期刊

第一作者： Lei, Kun

作者： Lei, Kun;Wei, Quanwei;Cheng, Ying;Wang, Zhe;Wu, Haoze;Shi, Fangxiong;Zhao, Fang;Ding, Wei

作者机构：

期刊名称：REPRODUCTION （ 影响因子：3.8； 五年影响因子：4.2 ）

ISSN： 1470-1626

年卷期： 2023 年 165 卷 4 期

页码：

收录情况： SCI

摘要： In brief The apoptosis of granulosa cells (GCs) is the main reason for porcine follicular atresia. This study provides a novel mechanism for peroxynitrite anion-mediated GC apoptosis and follicular atresia in porcine ovary. Abstract Granulosa cells play a crucial role in the development of follicles, and their cell apoptosis in the porcine ovary is a major contributor to follicular atresia. Here, we provide a new mechanism for follicular atresia by describing a crucial mechanism by which peroxynitrite anion (OONO-) may cause GC death. We discovered that nitric oxide, oxidative stress level, and OONO- were positively correlated with porcine follicular atresia, which was accompanied by high expression of matrix metalloproteinase 2 (MMP2) and MMP9. We created a model of OONO--induced apoptosis in GCs and discovered that OONO- could boost the expression of MMP2 and MMP9 and increase the expression of pro-apoptotic proteins and DNA damage. Furthermore, by inhibiting the activities of MMP2 and MMP9, we found that SB-3CT (a specific inhibitor for MMP2 and MMP9) alleviated the decrease in cell survival rates and DNA damage caused by OONO-, which may have been impacted by reducing the cleavage of PARP1 by MMP2 and MMP9. Therefore, our findings imply that OONO- can cause DNA damage to GCs, participating in mediating the expression of pro-apoptotic proteins and inhibiting DNA repair by preventing the activity of PARP1 through MMP2 and MMP9. These results help explain how OONO-/MMP2/MMP9 affects porcine follicular atresia and GC apoptosis.

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