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

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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The passage describes a new mechanism for follicular atresia, a condition where granulosa cells (GCs) in the porcine ovary undergo apoptosis, resulting in the degeneration of follicles. The mechanism involves the peroxynitrite anion (OONO-), which is associated with high levels of nitric oxide and oxidative stress, and is positively correlated with follicular atresia.

The authors conducted experiments to investigate the effect of OONO- on GCs and found that it can increase the expression of matrix metalloproteinase 2 (MMP2) and MMP9, which are enzymes involved in tissue remodeling. They also observed an increase in pro-apoptotic proteins and DNA damage in GCs exposed to OONO-.

To further understand the mechanism, the authors inhibited the activities of MMP2 and MMP9 using a specific inhibitor called SB-3CT. They found that the inhibitor could alleviate the decrease in cell survival rates and DNA damage caused by OONO-. They suggest that MMP2 and MMP9 may play a role in mediating the expression of pro-apoptotic proteins and inhibiting DNA repair by preventing the activity of PARP1, a protein involved in DNA repair.

Overall, the findings suggest that OONO-/MMP2/MMP9 affects porcine follicular atresia and GC apoptosis by causing DNA damage and inhibiting DNA repair. The study provides insights into the molecular mechanisms underlying follicular atresia and may contribute to the development of new treatments for the condition.

Related Products

Cat.No. Product Name Information
S7430 SB-3CT SB-3CT is an effective and selective gelatinase inhibitor with Ki of 13.9 nM and 600 nM for MMP-2 and MMP-9, respectively.

Related Targets

MMP