title: Oxidative stress activates AMPK in cultured cells primarily by increasing cellular AMP and/or ADP.
abstract: AMPK is known to be activated by oxidative stress. Addition of glucose oxidase to cells generates H2O2 at a constant rate that is opposed by enzymic degradation, providing a good model for physiological oxidative stress. AMPK activation by glucose oxidase correlated with increases in cellular AMP:ATP and was greatly reduced in cells expressing an AMP-insensitive AMPK mutant, although a small degree of activation remained. The effects of increased AMP were partly due to inhibition of Thr172 dephosphorylation. These results suggest that changes in adenine nucleotides, rather than direct oxidative modification, are the major drivers of AMPK activation during oxidative stress.
authors.affiliation: Division of Cell Signalling & Immunology, College of Life Sciences, University of Dundee, Dundee, DD1 5EH Scotland, UK.
authors.forename: F Romana
authors.initials: FR
authors.lastname: Auciello
authors.affiliation: Division of Cell Signalling & Immunology, College of Life Sciences, University of Dundee, Dundee, DD1 5EH Scotland, UK.
authors.forename: Fiona A
authors.initials: FA
authors.lastname: Ross
authors.affiliation: Division of Cell Signalling & Immunology, College of Life Sciences, University of Dundee, Dundee, DD1 5EH Scotland, UK.
authors.forename: Naoko
authors.initials: N
authors.lastname: Ikematsu
authors.affiliation: Division of Cell Signalling & Immunology, College of Life Sciences, University of Dundee, Dundee, DD1 5EH Scotland, UK. Electronic address: d.g.hardie@dundee.ac.uk.
authors.forename: D Grahame
authors.initials: DG
authors.lastname: Hardie
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism*; D004789:Enzyme Activation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D018384:Oxidative Stress; D011499:Protein Processing, Post-Translational
chemical_list: D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D006861:Hydrogen Peroxide; D055372:AMP-Activated Protein Kinases
keywords: ADP; AMP; AMP-activated protein kinase; Hydrogen peroxide; Oxidative stress
references.citation: J Biol Chem. 1995 Nov 10;270(45):27186-91
references.pmid: 7592975
references.citation: J Biol Chem. 2010 Oct 22;285(43):33154-33164
references.pmid: 20729205
references.citation: Cell Metab. 2013 Oct 1;18(4):546-55
references.pmid: 24093678
references.citation: Chem Biol. 2014 May 22;21(5):619-27
references.pmid: 24746562
references.citation: J Biol Chem. 2007 Oct 12;282(41):30107-19
references.pmid: 17711846
references.citation: FEBS Lett. 1996 Nov 18;397(2-3):347-51
references.pmid: 8955377
references.citation: Cell Metab. 2014 Feb 4;19(2):232-45
references.pmid: 24506865
references.citation: Curr Biol. 2003 Nov 11;13(22):2004-8
references.pmid: 14614828
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3329-35
references.pmid: 14985505
references.citation: J Biol Chem. 2002 May 3;277(18):15813-8
references.pmid: 11867640
references.citation: J Biol Chem. 2005 Aug 12;280(32):29060-6
references.pmid: 15980064
references.citation: Cell Metab. 2005 Jul;2(1):21-33
references.pmid: 16054096
references.citation: Cell Metab. 2013 Oct 1;18(4):556-66
references.pmid: 24093679
references.citation: J Biol Chem. 1992 Aug 25;267(24):16771-4
references.pmid: 1512218
references.citation: J Cell Sci. 2012 May 1;125(Pt 9):2115-25
references.pmid: 22619229
references.citation: Diabetes. 2013 Jul;62(7):2164-72
references.pmid: 23801715
references.citation: Biochem J. 2008 Nov 15;416(1):1-14
references.pmid: 18774945
references.citation: Biochem Biophys Res Commun. 2001 Sep 14;287(1):92-7
references.pmid: 11549258
references.citation: Genes Dev. 2005 Sep 1;19(17):1951-67
references.pmid: 16140981
references.citation: Nat Rev Mol Cell Biol. 2012 Mar 22;13(4):251-62
references.pmid: 22436748
references.citation: Chem Biol. 2012 Oct 26;19(10):1222-36
references.pmid: 23102217
references.citation: J Biol. 2003;2(4):28
references.pmid: 14511394
references.citation: Cell Metab. 2010 Jun 9;11(6):554-65
references.pmid: 20519126
references.citation: FEBS Lett. 1995 Dec 27;377(3):421-5
references.pmid: 8549768
references.citation: Cell Metab. 2005 Jul;2(1):9-19
references.pmid: 16054095
references.citation: Nature. 2011 Apr 14;472(7342):230-3
references.pmid: 21399626