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Resveratrol-induced p53 activation is associated with autophagy in mouse embryonic stem cells

Irina I Suvorova1, Aleksandra R Knyazeva2, Valery A Pospelov1

  • 1Institute of Cytology, Russian Academy of Sciences, St-Petersburg, Russian Federation.

Biochemical and Biophysical Research Communications
|August 13, 2018
PubMed

Insights

Resveratrol activates p53 in mouse embryonic stem cells (mESCs), but unlike in tumor cells, it stimulates autophagy rather than cell cycle arrest or apoptosis. This highlights a novel resveratrol-dependent p53 mechanism in mESCs.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Stem Cell Research

Background:

  • Resveratrol, a natural polyphenol, exhibits therapeutic effects, including p53-dependent cell cycle arrest and apoptosis in tumor cells.
  • Resveratrol-induced p53 activation is known to influence differentiation and apoptosis in embryonic stem cells (ESCs).

Purpose of the Study:

  • To investigate the mechanism of resveratrol-induced p53 activation in mouse embryonic stem cells (mESCs).
  • To determine the downstream effects of resveratrol-activated p53 in mESCs, specifically regarding cell cycle and apoptosis.

Main Methods:

  • Utilized mouse ESCs (mESCs) to study resveratrol's effects on p53.
  • Investigated the regulation of p53 by SIRT1 deacetylation and AMPK phosphorylation.
  • Analyzed p53's role in cell cycle progression, apoptosis, and autophagy, including dram1 gene expression.

Main Results:

  • Resveratrol activates p53 in mESCs, regulated by SIRT1 and AMPK.
  • Contrary to expectations, resveratrol-activated p53 did not induce G1/S cell cycle arrest or apoptosis in mESCs.
  • Resveratrol-activated p53 stimulated autophagy via transcriptional upregulation of the dram1 gene.

Conclusions:

  • Resveratrol activates p53 in mESCs through a mechanism involving SIRT1 and AMPK.
  • The study reveals a novel, non-canonical role for resveratrol-activated p53 in mESCs, promoting autophagy instead of cell cycle arrest or apoptosis.
  • This finding elucidates a unique resveratrol-dependent p53 pathway in embryonic stem cells, distinct from its effects in tumor cells.
Keywords:
AutophagyEmbryonic stem cellsPluripotencyResveratrolSIRT1p53

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