Neuroprotective signaling pathways are modulated by adenosine in the anoxia tolerant turtle.

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Gauri NayakSarah L Milton

Abstract

Cumulative evidence shows a protective role for adenosine A1 receptors (A1R) in hypoxia/ischemia; A1R stimulation reduces neuronal damage, whereas blockade exacerbates damage. The signal transduction pathways may involve the mitogen-activated protein kinase (MAPK) pathways and serine/threonine kinase (AKT), with cell survival depending on the timing and degree of upregulation of these cascades as well as the balance between pro-survival and pro-death pathways. Here, we show in vitro that extracellular signal-regulated kinase (ERK1/2) and phosphatidylinositol 3-kinase (PI3-K/AKT) activation is dependent on A1R stimulation, with further downstream effects that promote neuronal survival. Phosphorylated ERK1/2 (p-ERK) and AKT (p-AKT) as well as Bcl-2 are upregulated in anoxic neuronally enriched primary cultures from turtle brain. This native upregulation is further increased by the selective A1R agonist 2-chloro-N-cyclopentyladenosine (CCPA), whereas the selective antagonist 8-cyclopentyl-1,3-dihydropylxanthine (DPCPX) decreases p-ERK and p-AKT expression. Conversely, A1R antagonism resulted in increases in phosphorylated JNK (p-JNK), p38 (p-p38), and Bax. As pathological and adaptive changes occur simultaneously during anoxia/isc...Continue Reading

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Citations

Feb 8, 2014·Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology·Gina L J Galli, Jeffrey G Richards
Oct 27, 2015·Critical Care Medicine·Alexander Zarbock, John A Kellum
Mar 17, 2012·Bipolar Disorders·Alexander FanMark Hyman Rapaport
Jun 24, 2014·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Leila JahangardSerge Brand
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Jul 28, 2013·Brain Research Bulletin·Thomas I NathanielAdebobola I Nathaniel
Jan 31, 2015·Current Opinion in Anaesthesiology·Alexander ZarbockChristoph Schmidt
Mar 19, 2016·Experimental Physiology·Gauri NayakSarah L Milton
Jan 23, 2017·Progress in Neurobiology·Sijie LiXunming Ji
Sep 8, 2017·International Journal of Molecular Sciences·Laura Terraneo, Michele Samaja
Nov 3, 2017·The Journal of Experimental Biology·Sjannie LefevreGöran E Nilsson
Dec 7, 2013·Journal of the American Society of Nephrology : JASN·Natig GassanovFikret Er
Nov 8, 2014·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Göran E NilssonKåre-Olav Stensløkken
Dec 15, 2016·Purinergic Signalling·Filipe Marques GonçalvesRodrigo Bainy Leal
Mar 29, 2014·The Journal of Experimental Biology·John LarsonThomas J Park

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Methods Mentioned

BETA
protein assay

Software Mentioned

SPSS

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