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

文献类型： 外文期刊

作者： Lei, Kun 1 ; Wei, Quanwei 1 ; Cheng, Ying 1 ; Wang, Zhe 1 ; Wu, Haoze 1 ; Zhao, Fang 2 ; Ding, Wei 3 ; Shi, Fangxiong 1 ;

作者机构： 1.Nanjing Agr Univ, Coll Anim Sci & Technol, Nanjing, Peoples R China

2.Jiangsu Acad Agr Sci, Inst Anim Sci, Nanjing, Peoples R China

3.Anim Husb & Vet Coll, Jiangsu Vocat Coll Agr & Forestry, Jurong, Peoples R China

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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