NCX1 Exchanger Cooperates with Calretinin to Confer Preconditioning-Induced Tolerance Against Cerebral Ischemia in the Striatum

Francesca Boscia, Antonella Casamassa, Agnese Secondo, Alba Esposito, Anna Pannaccione, Rossana Sirabella, Giuseppe Pignataro, Ornella Cuomo, Antonio Vinciguerra, Valeria de Rosa, Lucio Annunziato

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1365-1376
Number of pages12
JournalMolecular Neurobiology
Volume53
Issue number2
DOIs
Publication statusPublished - Mar 1 2016

Keywords

  • Calretinin
  • Cerebral ischemia
  • Na/Ca exchanger
  • NCX1
  • Preconditioning
  • Tolerance

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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