Concurrent regulation of AMP-activated protein kinase and SIRT1 in mammalian cells

Gabriela Suchankova, Lauren E. Nelson, Zachary Gerhart-Hines, Meghan Kelly, Marie Soleil Gauthier, Asish K. Saha, Yasuo Ido, Pere Puigserver, Neil B. Ruderman

Research output: Contribution to journalArticle

Abstract

We examined in HepG2 cells whether glucose-induced changes in AMP-activated protein kinase (AMPK) activity could be mediated by SIRT1, an NAD+-dependent histone/protein deacetylase that has been linked to the increase in longevity caused by caloric restriction. Incubation with 25 vs. 5 mM glucose for 6 h concurrently diminished the phosphorylation of AMPK (Thr 172) and ACC (Ser 79), increased lactate release, and decreased the abundance and activity of SIRT1. In contrast, incubation with pyruvate (0.1 and 1 mM) for 2 h increased AMPK phosphorylation and SIRT1 abundance and activity. The putative SIRT1 activators resveratrol and quercetin also increased AMPK phosphorylation. None of the tested compounds (low or high glucose, pyruvate, and resveratrol) significantly altered the AMP/ATP ratio. Collectively, these findings raise the possibility that glucose-induced changes in AMPK are linked to alterations in SIRT1 abundance and activity and possibly cellular redox state.

Original languageEnglish (US)
Pages (from-to)836-841
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume378
Issue number4
DOIs
StatePublished - Jan 23 2009
Externally publishedYes

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Keywords

  • AMPK
  • Redox state
  • Resveratrol
  • SIRT1

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Suchankova, G., Nelson, L. E., Gerhart-Hines, Z., Kelly, M., Gauthier, M. S., Saha, A. K., Ido, Y., Puigserver, P., & Ruderman, N. B. (2009). Concurrent regulation of AMP-activated protein kinase and SIRT1 in mammalian cells. Biochemical and Biophysical Research Communications, 378(4), 836-841. https://doi.org/10.1016/j.bbrc.2008.11.130