1. Academic Validation
  2. Role of the SIRT1/p53 regulatory axis in oxidative stress‑mediated granulosa cell apoptosis

Role of the SIRT1/p53 regulatory axis in oxidative stress‑mediated granulosa cell apoptosis

  • Mol Med Rep. 2021 Jan;23(1):20. doi: 10.3892/mmr.2020.11658.
Sang-Ah Park  # 1 Na-Rae Joo  # 1 Jung-Hwan Park 1 Sang-Muk Oh 1
Affiliations

Affiliation

  • 1 Department of Biochemistry, Priority Research Center, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea.
  • # Contributed equally.
Abstract

Oxidative stress has been suggested to induce granulosa cell Apoptosis, which contributes to follicular atresia. However, the mechanism via which oxidative stress mediates granulosa cell Apoptosis remains elusive. Therefore, the aim of this study was to elucidate the molecular mechanisms regulating oxidative stress‑induced granulosa cell Apoptosis. The present study demonstrated that Reactive Oxygen Species induced by H2O2 resulted in human granulosa COV434 cell Apoptosis via the regulation of Sirtuin 1 (SIRT1)‑mediated p53 activity. Endogenous SIRT1 expression was alleviated by H2O2 treatment of COV434 cells in a time‑dependent manner. In addition, knockdown or inhibition of SIRT1 promoted H2O2‑induced poly(ADP‑ribose) polymerase (PARP) cleavage and p53 acetylation, which led to an increase in COV434 cell Apoptosis. Treatment with H2O2 enhanced the expression levels of the p53‑dependent proteins, p53‑upregulated modulator of Apoptosis (PUMA) and phorbol‑12‑myristate‑13‑acetate‑induced protein 1 (PMAIP1), as well as those of p53; however, knockdown of p53 decreased cleaved PARP, PUMA and PMAIP1 expression levels induced by H2O2 treatment. Moreover, knockdown of PUMA or PMAIP1 attenuated the H2O2 induction of PARP cleavage and COV434 cell Apoptosis. In conclusion, the present findings suggested that H2O2‑induced oxidative stress causes granulosa COV434 cell Apoptosis via the upregulation of p53 activity by SIRT1 suppression, indicating a mechanistic role of the SIRT1/p53 axis in H2O2‑induced granulosa cell Apoptosis.

Keywords

granulosa cell; oxidative stress; sirtuin 1; p53; apoptosis.

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