TY - JOUR
T1 - Concurrent regulation of AMP-activated protein kinase and SIRT1 in mammalian cells
AU - Suchankova, Gabriela
AU - Nelson, Lauren E.
AU - Gerhart-Hines, Zachary
AU - Kelly, Meghan
AU - Gauthier, Marie Soleil
AU - Saha, Asish K.
AU - Ido, Yasuo
AU - Puigserver, Pere
AU - Ruderman, Neil B.
PY - 2009/1/23
Y1 - 2009/1/23
N2 - 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.
AB - 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.
KW - AMPK
KW - Redox state
KW - Resveratrol
KW - SIRT1
UR - http://www.scopus.com/inward/record.url?scp=57849131142&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=57849131142&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2008.11.130
DO - 10.1016/j.bbrc.2008.11.130
M3 - Article
C2 - 19071085
AN - SCOPUS:57849131142
SN - 0006-291X
VL - 378
SP - 836
EP - 841
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -