title: NCX1 Exchanger Cooperates with Calretinin to Confer Preconditioning-Induced Tolerance Against Cerebral Ischemia in the Striatum.
abstract: Recently, the Na(+)/Ca(+2) exchanger NCX1 and the calcium binding protein calretinin have emerged as new molecular effectors of delayed preconditioning in the brain. In the present study, we investigated whether NCX1 and calretinin cooperate within the preconditioned striatum to confer neurons greater resistance to degeneration. Confocal microscopy analysis revealed that NCX1 expression was upregulated in calretinin-positive interneurons in the rat striatum after tolerance induction. Consistently, coimmunoprecipitation assays performed on human SHSY-5Y cells, a neuronal cell line which constitutively expresses calretinin, revealed a binding between NCX1 and calretinin. Finally, silencing of calretinin expression, both in vitro and in vivo, significantly prevented preconditioning-induced neuroprotection. Interestingly, our biochemical and functional studies showed that the selective silencing of calretinin in brain cells significantly prevented not only the preconditioning-induced upregulation of NCX1 expression and activity but also the activation of the prosurvival protein kinase Akt, which is involved in calretinin and NCX1 protective actions. Collectively, our results indicate that the Na(+)/Ca(+2) exchanger NCX1 and the calcium binding protein calretinin cooperate within the striatum to confer tolerance against cerebral ischemia.
authors: Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine, Federico II University of Naples, Naples, Italy.
authors: Francesca
authors: F
authors: Boscia
authors: Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine, Federico II University of Naples, Naples, Italy.
authors: Antonella
authors: A
authors: Casamassa
authors: Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine, Federico II University of Naples, Naples, Italy.
authors: Agnese
authors: A
authors: Secondo
authors: Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine, Federico II University of Naples, Naples, Italy.
authors: Alba
authors: A
authors: Esposito
authors: Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine, Federico II University of Naples, Naples, Italy.
authors: Anna
authors: A
authors: Pannaccione
authors: Fondazione IRCSS SDN, Naples, Italy.
authors: Rossana
authors: R
authors: Sirabella
authors: Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine, Federico II University of Naples, Naples, Italy.
authors: Giuseppe
authors: G
authors: Pignataro
authors: Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine, Federico II University of Naples, Naples, Italy.
authors: Ornella
authors: O
authors: Cuomo
authors: Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine, Federico II University of Naples, Naples, Italy.
authors: Antonio
authors: A
authors: Vinciguerra
authors: Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine, Federico II University of Naples, Naples, Italy.
authors: Valeria
authors: V
authors: de Rosa
authors: Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine, Federico II University of Naples, Naples, Italy. lannunzi@unina.it.|Fondazione IRCSS SDN, Naples, Italy. lannunzi@unina.it.
authors: Lucio
authors: L
authors: Annunziato
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D064032:Calbindin 2 / Q000378:metabolism*; D045744:Cell Line, Tumor; D020868:Gene Silencing; D006801:Humans; D047468:Immunoprecipitation; D007395:Interneurons / Q000378:metabolism; D019194:Ischemic Preconditioning; D008297:Male; D017072:Neostriatum / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D000066829:Neuroprotection; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D064032:Calbindin 2; D019831:Sodium-Calcium Exchanger; D051057:Proto-Oncogene Proteins c-akt
keywords: Calretinin; Cerebral ischemia; NCX1; Na/Ca+2 exchanger; Preconditioning; Tolerance
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