title: The NCX3 isoform of the Na+/Ca2+ exchanger contributes to neuroprotection elicited by ischemic postconditioning.
abstract: It has been recently shown that a short sublethal brain ischemia subsequent to a prolonged harmful ischemic episode may confer ischemic neuroprotection, a phenomenon termed ischemic postconditioning. Na(+)/Ca(2+) exchanger (NCX) isoforms, NCX1, NCX2, and NCX3, are plasma membrane ionic transporters widely distributed in the brain and involved in the control of Na(+) and Ca(2+) homeostasis and in the progression of stroke damage. The objective of this study was to evaluate the role of these three proteins in the postconditioning-induced neuroprotection. The NCX protein and mRNA expression was evaluated at different time points in the ischemic temporoparietal cortex of rats subjected to tMCAO alone or to tMCAO plus ischemic postconditioning. The results of this study showed that NCX3 protein and ncx3 mRNA were upregulated in those brain regions protected by postconditioning treatment. These changes in NCX3 expression were mediated by the phosphorylated form of the ubiquitously expressed serine/threonine protein kinase p-AKT, as the p-AKT inhibition prevented NCX3 upregulation. The relevant role of NCX3 during postconditioning was further confirmed by results showing that NCX3 silencing, induced by intracerebroventricular infusion of small interfering RNA (siRNA), partially reverted the postconditioning-induced neuroprotection. The results of this study support the idea that the enhancement of NCX3 expression and activity might represent a reasonable strategy to reduce the infarct extension after stroke.
authors.affiliation: Division of Pharmacology, Department of Neuroscience, School of Medicine, Federico II University of Naples, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pignataro
authors.forename: Elga
authors.initials: E
authors.lastname: Esposito
authors.forename: Ornella
authors.initials: O
authors.lastname: Cuomo
authors.forename: Rossana
authors.initials: R
authors.lastname: Sirabella
authors.forename: Francesca
authors.initials: F
authors.lastname: Boscia
authors.forename: Natascia
authors.initials: N
authors.lastname: Guida
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Di Renzo
authors.forename: Lucio
authors.initials: L
authors.lastname: Annunziato
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002544:Cerebral Infarction / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D057967:Infusions, Intraventricular; D002546:Ischemic Attack, Transient / Q000235:genetics* / Q000628:therapy*; D057775:Ischemic Postconditioning; D007536:Isomerism; D008297:Male; D018613:Microscopy, Confocal; D009025:Morpholines / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C110927:Slc8a2 protein, rat; C491102:Slc8a3 protein, rat; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt