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

Biochem Biophys Res Commun. 2018 Sep 10;503(3):2180-2185. doi: 10.1016/j.bbrc.2018.08.010. Epub 2018 Aug 8.

Abstract

Resveratrol is a natural polyphenol with several therapeutic effects, in particular, inducing p53-dependent cell cycle arrest and/or apoptosis in tumor cells. Resveratrol-induced p53 activation may trigger differentiation and apoptosis in embryonic stem cells (ESCs). We show that resveratrol activates p53 that is negatively regulated by SIRT1 deacetylation on Lys379 and positively by AMPK phosphorylation on Ser15 in mouse ESCs (mESCs). Surprisingly, the resveratrol-activated p53 is not associated with either G1/S cell cycle checkpoint or apoptosis in mESCs. Instead, it stimulates autophagy in a transcriptional-dependent manner involving up-regulation of dram1 gene expression. This study demonstrates a novel mechanism of resveratrol-dependent p53 activation in mESCs.

Keywords: Autophagy; Embryonic stem cells; Pluripotency; Resveratrol; SIRT1; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / drug effects*
  • Cell Cycle Checkpoints / drug effects
  • Cells, Cultured
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mouse Embryonic Stem Cells / cytology*
  • Mouse Embryonic Stem Cells / drug effects*
  • Mouse Embryonic Stem Cells / metabolism
  • Resveratrol / pharmacology*
  • Tumor Suppressor Protein p53 / agonists*
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation / drug effects

Substances

  • DRAM-1 protein, mouse
  • Membrane Proteins
  • Tumor Suppressor Protein p53
  • Resveratrol