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

Sang-Ah Park1, Na-Rae Joo1, Jung-Hwan Park1

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

Molecular Medicine Reports
|November 12, 2020
PubMed

Insights

Hydrogen peroxide (H2O2) induces granulosa cell apoptosis by suppressing sirtuin 1 (SIRT1) and activating p53. This SIRT1/p53 pathway is key to oxidative stress-related follicular atresia.

Area of Science:

  • Reproductive Biology
  • Cellular Stress Response
  • Molecular Mechanisms of Apoptosis

Background:

  • Oxidative stress is implicated in granulosa cell apoptosis and follicular atresia.
  • The precise molecular pathways linking oxidative stress to granulosa cell apoptosis are not fully understood.

Purpose of the Study:

  • To investigate the molecular mechanisms by which oxidative stress induces apoptosis in human granulosa cells.
  • To elucidate the role of sirtuin 1 (SIRT1) and p53 in this process.

Main Methods:

  • Utilized human granulosa COV434 cells treated with hydrogen peroxide (H2O2) to induce oxidative stress.
  • Assessed apoptosis, poly(ADP-ribose) polymerase (PARP) cleavage, p53 acetylation, and expression of SIRT1, p53, PUMA, and PMAIP1.
  • Employed gene knockdown techniques for SIRT1, p53, PUMA, and PMAIP1.

Main Results:

  • H2O2-induced oxidative stress led to COV434 cell apoptosis.
  • SIRT1 expression was downregulated by H2O2 in a time-dependent manner.
  • Knockdown of SIRT1 enhanced H2O2-induced apoptosis by promoting PARP cleavage and p53 acetylation.
  • H2O2 upregulated p53, p53-upregulated modulator of apoptosis (PUMA), and phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) expression.
  • Knockdown of p53, PUMA, or PMAIP1 attenuated H2O2-induced apoptosis.

Conclusions:

  • H2O2-induced oxidative stress triggers granulosa cell apoptosis through SIRT1 suppression and subsequent p53 activation.
  • The SIRT1/p53 signaling axis plays a critical role in mediating oxidative stress-induced granulosa cell apoptosis.
Keywords:
granulosa celloxidative stresssirtuin 1p53apoptosis

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