'Mild mitochondrial uncoupling' induced protection against neuronal excitotoxicity requires AMPK activity

Biochimica Et Biophysica Acta
Petronela WeisováManus W Ward

Abstract

The preconditioning response conferred by a mild uncoupling of the mitochondrial membrane potential (Δψ(m)) has been attributed to altered reactive oxygen species (ROS) production and mitochondrial Ca(2+) uptake within the cells. Here we have explored if altered cellular energetics in response to a mild mitochondrial uncoupling stimulus may also contribute to the protection. The addition of 100 nM FCCP for 30 min to cerebellar granule neurons (CGNs) induced a transient depolarization of the Δψ(m), that was sufficient to significantly reduce CGN vulnerability to the excitotoxic stimulus, glutamate. On investigation, the mild mitochondrial 'uncoupling' stimulus resulted in a significant increase in the plasma membrane levels of the glucose transporter isoform 3, with a hyperpolarisation of Δψ(m) and increased cellular ATP levels also evident following the washout of FCCP. Furthermore, the phosphorylation state of AMP-activated protein kinase (AMPK) (Thr 172) was increased within 5 min of the uncoupling stimulus and elevated up to 1h after washout. Significantly, the physiological changes and protection evident after the mild uncoupling stimulus were lost in CGNs when AMPK activity was inhibited. This study identifies an additiona...Continue Reading

References

Oct 17, 2001·The Journal of Clinical Investigation·G ZhouD E Moller
Dec 4, 2001·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·C PeraltaJ Roselló-Catafau
Jun 6, 2003·Biochemical Pharmacology·Tamas L HorvathColin Barnstable
Apr 20, 2004·European Journal of Pharmacology·Bruce S McEwen, Lawrence P Reagan
Aug 12, 2004·Free Radical Biology & Medicine·Martin D BrandNadeene Parker
Feb 18, 2005·Journal of Neurochemistry·Manus W WardChristopher N Connolly
Oct 15, 2005·Nature Reviews. Neuroscience·Zane B AndrewsTamas L Horvath
Jul 6, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Nagendra Yadava, David G Nicholls
Aug 3, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Manus W WardJochen H M Prehn
May 29, 2008·Aging Cell·Camille C Caldeira da SilvaAlicia J Kowaltowski
Feb 26, 2009·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Suresh L Mehta, P Andy Li
Mar 6, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Petronela WeisováManus W Ward
Apr 11, 2009·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Milos R SpasićKoenraad K Norga
May 7, 2009·Journal of Neurochemistry·Gabriele V RonnettSusan Aja
May 16, 2009·Mechanisms of Ageing and Development·Bernard D LemireDana Gásková
Jun 23, 2009·Nature Reviews. Neuroscience·Lorenzo GalluzziGuido Kroemer
Aug 1, 2009·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jeroen PoelsKoenraad K Norga
Sep 18, 2009·Pflügers Archiv : European journal of physiology·Marcelo O Dietrich, Tamas L Horvath
Dec 17, 2009·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Jun Li, Louise D McCullough
Mar 31, 2010·The Journal of Cell Biology·Caoimhín G ConcannonJochen H M Prehn
Aug 18, 2010·Antioxidants & Redox Signaling·Petronela WeisováJochen H M Prehn
Jan 25, 2011·Nature Cell Biology·Joungmok KimKun-Liang Guan

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Citations

Jan 20, 2015·Journal of Neurochemistry·Catherine I RoussetClaire Thornton
Sep 30, 2014·Journal of Bioenergetics and Biomembranes·Niamh M C Connolly, Jochen H M Prehn
Aug 31, 2014·Journal of Bioenergetics and Biomembranes·David G NichollsAkos A Gerencser
Mar 6, 2017·Biochemistry. Biokhimii︠a︡·D A Knorre, F F Severin
Feb 3, 2018·Oxidative Medicine and Cellular Longevity·Jingdian ZhangYing Zhang
Jul 6, 2014·Physiological Reviews·Dmitry B ZorovSteven J Sollott
Mar 7, 2013·Journal of Neuroscience Research·Bharti Manwani, Louise D McCullough
Sep 7, 2016·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·John G GeislerMark P Mattson
Jun 24, 2017·Apoptosis : an International Journal on Programmed Cell Death·A BobbaA Atlante
Mar 24, 2017·Neuronal Signaling·Claire Thornton
Dec 24, 2019·Molecular Aspects of Medicine·Luiz H M BoziJulio C B Ferreira
Aug 21, 2021·Environmental Toxicology and Chemistry·You Song, Daniel L Villeneuve

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