Concurrent regulation of AMP-activated protein kinase and SIRT1 in mammalian cells.
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. 5mM glucose for 6h 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 1mM) for 2h 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.
Suchankova
Gabriela
G
Department of Medicine, Section of Endocrinology, Boston Medical Center, Boston, MA 02118, USA.
Nelson
Lauren E
LE
Gerhart-Hines
Zachary
Z
Kelly
Meghan
M
Gauthier
Marie-Soleil
MS
Saha
Asish K
AK
Ido
Yasuo
Y
Puigserver
Pere
P
Ruderman
Neil B
NB
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology; D010084:Oxidation-Reduction; D010766:Phosphorylation / Q000187:drug effects; D019289:Pyruvic Acid / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D000077185:Resveratrol; D012694:Serine / Q000378:metabolism; D056564:Sirtuin 1; D037761:Sirtuins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology; D013912:Threonine / Q000378:metabolism
D013267:Stilbenes; D009536:Niacinamide; D013912:Threonine; D000249:Adenosine Monophosphate; D012694:Serine; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D011794:Quercetin; D055372:AMP-Activated Protein Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins; D005947:Glucose; D000077185:Resveratrol