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TOPK inhibits TNF-α-induced granulosa cell apoptosis via regulation of SIRT1/p53

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

  • 1Department of Biochemistry, College of Medicine, Konyang University, Daejeon, 35365, South Korea.

Biochemical and Biophysical Research Communications
|May 6, 2023
PubMed

Insights

T-LAK cell originated protein kinase (TOPK) inhibits TNF-α-induced apoptosis in human granulosa cells. TOPK regulates the p53/SIRT1 axis, suggesting a role in ovarian follicle development.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Reproductive Biology

Background:

  • T-LAK cell originated protein kinase (TOPK) is implicated in cancer cell proliferation and migration.
  • The function of TOPK within the ovarian follicle microenvironment is currently undefined.

Purpose of the Study:

  • To investigate the role of TOPK in TNF-α-induced apoptosis of human granulosa cells (COV434).
  • To elucidate the molecular mechanisms by which TOPK influences granulosa cell survival.

Main Methods:

  • Cultured human granulosa COV434 cells were treated with TNF-α.
  • TOPK expression and activity were modulated using inhibitors and genetic approaches.
  • Expression levels of SIRT1, p53, p53 acetylation, and pro-apoptotic factors (PUMA, NOXA) were analyzed.
  • SIRT1 transcriptional activity was assessed.

Main Results:

  • TOPK expression increased in response to TNF-α in COV434 cells.
  • TOPK inhibition decreased TNF-α-induced SIRT1 expression and attenuated its transcriptional activity.
  • TOPK inhibition promoted p53 acetylation and increased the expression of PUMA and NOXA.
  • SIRT1 inhibition exacerbated TNF-α-induced p53 acetylation and PUMA/NOXA expression, leading to apoptosis.

Conclusions:

  • TOPK suppresses TNF-α-induced apoptosis in COV434 granulosa cells through the p53/SIRT1 signaling pathway.
  • TOPK plays a protective role in granulosa cells against TNF-α-mediated cell death.
  • These findings suggest TOPK is a potential regulator of ovarian follicular development.
Keywords:
ApoptosisGranulosa cellTNF-αTOPK

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