ABSTRACT
Title
NCX as a key player in the neuroprotection exerted by ischemic preconditioning and postconditioning
Authors
G. Pignataro, E. Esposito, R. Sirabella, F. Boscia, O. Cuomo, A. Vinciguerra, G.F. Di Renzo, L. Annunziato
Division Pharmacology, Department Neuroscience, School of Medicine, Federico II University of Naples, Italy
Division Pharmacology, Department Neuroscience, School of Medicine, Federico II University of Naples, Italy
Abstract
Ischemic preconditioning is a neuroprotective mechanism in which a brief non-injurious episode of ischemia protects the brain from a subsequent lethal insult.
Recently, it has been reported that modified reperfusion subsequent to a prolonged ischemic episode may also confer neuroprotection, a phenomenon termed postconditioning.
Mitogen Activated Kinases (MAPK) play a key role in these neuroprotective mechanisms.
Objectives of this study was to evaluate whether Na+/Ca2+ exchangers (NCXs), a family of ionic transporters that contribute to the maintenance of intracellular ionic homeostasis, contribute to the progression of the ischemic lesion.
Results of this study indicated that: (1) NCX1 and NCX3 are up-regulated in those brain regions protected by preconditioning; while (2) postconditioning treatment induces an up-regulation only in NCX3 expression. (3) The changes observed in the expression of these proteins seems to be due to p-AKT. In fact, p-AKT inhibition reverted the preconditioning and postconditioning neuroprotective effect and prevented NCXs overexpression. (4) The involvement of NCX in preconditioning and postconditioning neuroprotection is further highlighted by the results of experiments showing that a partial reversion of the protective effect induced by preconditioning was obtained by silencing NCX1 or NCX3 while the silencing of NCX3 was able to mitigate the protection induced by ischemic postconditioning.
Altogether the data presented here suggest that NCX1 and NCX3 represent two promising druggable targets for setting on new strategies in stroke therapy.
Recently, it has been reported that modified reperfusion subsequent to a prolonged ischemic episode may also confer neuroprotection, a phenomenon termed postconditioning.
Mitogen Activated Kinases (MAPK) play a key role in these neuroprotective mechanisms.
Objectives of this study was to evaluate whether Na+/Ca2+ exchangers (NCXs), a family of ionic transporters that contribute to the maintenance of intracellular ionic homeostasis, contribute to the progression of the ischemic lesion.
Results of this study indicated that: (1) NCX1 and NCX3 are up-regulated in those brain regions protected by preconditioning; while (2) postconditioning treatment induces an up-regulation only in NCX3 expression. (3) The changes observed in the expression of these proteins seems to be due to p-AKT. In fact, p-AKT inhibition reverted the preconditioning and postconditioning neuroprotective effect and prevented NCXs overexpression. (4) The involvement of NCX in preconditioning and postconditioning neuroprotection is further highlighted by the results of experiments showing that a partial reversion of the protective effect induced by preconditioning was obtained by silencing NCX1 or NCX3 while the silencing of NCX3 was able to mitigate the protection induced by ischemic postconditioning.
Altogether the data presented here suggest that NCX1 and NCX3 represent two promising druggable targets for setting on new strategies in stroke therapy.