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

doi:10.1016/j.bbrc.2008.11.130

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^*

^*Corresponding author af dette arbejde

Gerhart-Hines Group

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

150 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Biochemical and Biophysical Research Communications
Vol/bind	378
Udgave nummer	4
Sider (fra-til)	836-841
Antal sider	6
ISSN	0006-291X
DOI	https://doi.org/10.1016/j.bbrc.2008.11.130
Status	Udgivet - 23 jan. 2009

Bibliografisk note

Funding Information:
This work was supported by NIH Grants R01 DK19514, P01 HL08758, and DK67509 (N.R.). G.S. was the recipient of a mentor based grant from the ADA (N.R.). L.N. was supported by NIH Training Grant T32DK07201-31 and a Fellowship Award F30DK082136 from NIDDK. The authors would like to thank Jose Cacicedo and Fan Lan for helpful comments and technical advice.

Adgang til dokumentet

10.1016/j.bbrc.2008.11.130

Citationsformater

Concurrent regulation of AMP-activated protein kinase and SIRT1 in mammalian cells. / Suchankova, Gabriela; Nelson, Lauren E.; Gerhart-Hines, Zachary; Kelly, Meghan; Gauthier, Marie Soleil; Saha, Asish K.; Ido, Yasuo; Puigserver, Pere; Ruderman, Neil B.

I: Biochemical and Biophysical Research Communications, Bind 378, Nr. 4, 23.01.2009, s. 836-841.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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title = "Concurrent regulation of AMP-activated protein kinase and SIRT1 in mammalian cells",

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.",

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

note = "Funding Information: This work was supported by NIH Grants R01 DK19514, P01 HL08758, and DK67509 (N.R.). G.S. was the recipient of a mentor based grant from the ADA (N.R.). L.N. was supported by NIH Training Grant T32DK07201-31 and a Fellowship Award F30DK082136 from NIDDK. The authors would like to thank Jose Cacicedo and Fan Lan for helpful comments and technical advice.",

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AU - Gauthier, Marie Soleil

AU - Saha, Asish K.

AU - Ido, Yasuo

AU - Puigserver, Pere

AU - Ruderman, Neil B.

N1 - Funding Information: This work was supported by NIH Grants R01 DK19514, P01 HL08758, and DK67509 (N.R.). G.S. was the recipient of a mentor based grant from the ADA (N.R.). L.N. was supported by NIH Training Grant T32DK07201-31 and a Fellowship Award F30DK082136 from NIDDK. The authors would like to thank Jose Cacicedo and Fan Lan for helpful comments and technical advice.

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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.

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