AMP-activated protein kinase (AMPK) activating agents cause dephosphorylation of Akt and glycogen synthase kinase-3.

Biochemical Pharmacology
Taj D KingRichard S Jope

Abstract

AMP-activated protein kinase (AMPK) is a key cellular sensor of reduced energy supply that is activated by increases in the cellular ratio of AMP/ATP. Phenformin and 5-aminoimidazole-4-carboxamide riboside (AICAR) are two drugs widely used to activate AMPK experimentally. In both differentiated hippocampal neurons and neuroblastoma SH-SY5Y cells we found that these two agents not only activated AMPK, but conversely greatly reduced the activating Ser/Thr phosphorylation of Akt. This blockade of Akt activity consequently lowered the inhibitory serine-phosphorylation of its substrates, glycogen synthase kinase-3alpha/beta (GSK3alpha/beta). An inhibitor of AMPK (Compound C) did not block dephosphorylation of Akt and GSK3. Thus, both drugs widely used to activate AMPK also caused dephosphorylation of Akt and of GSK3. The mechanism for Akt dephosphorylation caused by phenformin, but not AICAR, was due to inhibition of growth factor-induced signaling that leads to Akt phosphorylation. Stimulation of muscarinic receptors with carbachol in SH-SY5Y cells also activated AMPK and transiently caused dephosphorylation of Akt. These findings show that Akt dephosphorylation often occurs concomitantly with AMPK activation when cells are treated...Continue Reading

References

Apr 1, 1995·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·N HeninG Van den Berghe
Sep 28, 2000·Biochemical and Biophysical Research Communications·K KishiY Ebina
Aug 18, 2001·Journal of Applied Physiology·W W Winder
Aug 31, 2001·Progress in Neurobiology·C A Grimes, R S Jope
Oct 17, 2001·The Journal of Clinical Investigation·G ZhouD E Moller
Jun 6, 2002·Proceedings of the National Academy of Sciences of the United States of America·Piyajit WatcharasitRichard S Jope
Mar 11, 2003·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Sarah L LongnusMichael F Allard
Nov 15, 2003·Current Biology : CB·Angela WoodsDavid Carling
Jan 10, 2004·Journal of Neurochemistry·Gautam N Bijur, Richard S Jope
Jan 20, 2004·Trends in Biochemical Sciences·David Carling
Feb 13, 2004·American Journal of Physiology. Cell Physiology·Lubna Al-KhaliliAnna Krook
Apr 8, 2004·American Journal of Physiology. Endocrinology and Metabolism·Kei SakamotoDario R Alessi
Apr 23, 2004·Trends in Biochemical Sciences·Richard S Jope, Gail V W Johnson
May 20, 2004·American Journal of Physiology. Endocrinology and Metabolism·Lubna Al-KhaliliGregory D Cartee
Oct 29, 2004·Journal of Cell Science·D Grahame Hardie
Mar 18, 2005·The Journal of Biological Chemistry·Louise D McCulloughGabriele V Ronnett

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Citations

Mar 17, 2010·Cardiovascular Drugs and Therapy·Marta A PaivaMihaela M Mocanu
Nov 19, 2010·American Journal of Physiology. Cell Physiology·Heather M ArgadineGary C Sieck
Oct 30, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ru-Jeng TengGirija G Konduri
Oct 1, 2011·American Journal of Physiology. Renal Physiology·Wilfred LieberthalJerrold S Levine
Feb 20, 2010·Journal of Molecular Signaling·Rong TaoZhijun Luo
Jan 28, 2014·PloS One·W Keith MiskiminsJoon Young Choi
Mar 1, 2012·Neuromolecular Medicine·Zhiyou CaiBin Zhao
Sep 29, 2011·International Journal of Radiation Oncology, Biology, Physics·Sofie F IsebaertKarin M Haustermans
May 3, 2011·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·Pingwen XuD Michael Denbow
Nov 10, 2009·Biochemical Pharmacology·Celina García-GarcíaAbelardo López-Rivas
May 12, 2009·Neuroscience Letters·Steven J GrecoNikolaos Tezapsidis
Mar 26, 2009·Journal of Molecular and Cellular Cardiology·Sabzali JavadovMorris Karmazyn
Jan 27, 2009·Biochemical and Biophysical Research Communications·Steven J GrecoNikolaos Tezapsidis
Apr 6, 2016·Heliyon·Larry D SpearsJonathan S Fisher
Mar 19, 2008·Journal of Cellular Biochemistry·Barbara E Slack, Jan K Blusztajn
Nov 13, 2008·Journal of Cellular Biochemistry·Jacqueline VazquezMary Ann Greco
Dec 22, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Alessandra CaligiuriFabio Marra
Mar 31, 2011·Journal of Neurochemistry·Dana S HutchinsonMarie E Gibbs
Aug 15, 2012·Immunological Reviews·Katelin N TownsendJulian J Lum
Jun 27, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·S YueY Zhai
Apr 8, 2014·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Hao TangJing-Yan Han
Jun 7, 2014·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·J RaoY Zhai
Nov 2, 2014·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·J RaoL Lu
Jun 6, 2012·International Journal of Alzheimer's Disease·Lap HoGiulio Maria Pasinetti
Mar 4, 2008·Molecular and Cellular Endocrinology·Olorunseun O Ogunwobi, Ian L P Beales
Jan 10, 2012·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Toran SanliTheodoros Tsakiridis

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