The silencing in PC-12 cells or the knocking-out in mice of the ncx3 gene, that encodes for the Na+/Ca2+ exchanger type 3, prevented the enhancement of both I(NCX) and Ca(2+) content in ER stores induced by beta -amyloid 1-42, suggesting that NCX3 was involved in the increase of ER Ca(2+) content stimulated by this peptide. By contrast, in the late phase (72 h), when the NCX3 proteolytic cleavage abruptly decreased, the occurrence of a parallel reduction in ER Ca(2+) content triggered ER stress, as revealed by caspase-12 activation. Concomitantly, the late increase in [Ca(2+)](i) coincided with neuronal death. Interestingly, NCX3 silencing caused an earlier activation of Aβ(1-42)-induced caspase-12. Indeed, in NCX3-silenced neurons, Aβ(1-42) exposure hastened caspase-dependent apoptosis, thus reinforcing neuronal cell death. These results suggest that Aβ(1-42), through Ca(2+)-dependent calpain activation, generates a hyperfunctional form of the Na+/Ca2+ exchanger NCX3 that, by increasing Ca(2+) content into ER, delays caspase-12 activation and thusER-stress and neuronal death.

A new concept: Aβ1-42 generates a hyperfunctional proteolytic NCX3 fragment that delays caspase-12 activation and neuronal death / Pannaccione, Anna; Secondo, Agnese; Molinaro, Pasquale; D'Avanzo, C; Cantile, M; Esposito, A; Boscia, Francesca; Scorziello, Antonella; Sirabella, Rossana; Sokolow, S; Herchuelz, A; DI RENZO, GIANFRANCO MARIA LUIGI; Annunziato, Lucio. - In: THE JOURNAL OF NEUROSCIENCE. - ISSN 0270-6474. - 32:(2012), pp. 10609-10617. [10.1523/JNEUROSCI.5031-12.2012]

A new concept: Aβ1-42 generates a hyperfunctional proteolytic NCX3 fragment that delays caspase-12 activation and neuronal death

PANNACCIONE, ANNA;SECONDO, AGNESE;MOLINARO, PASQUALE;BOSCIA, FRANCESCA;SCORZIELLO, ANTONELLA;SIRABELLA, ROSSANA;DI RENZO, GIANFRANCO MARIA LUIGI;ANNUNZIATO, LUCIO
2012

Abstract

The silencing in PC-12 cells or the knocking-out in mice of the ncx3 gene, that encodes for the Na+/Ca2+ exchanger type 3, prevented the enhancement of both I(NCX) and Ca(2+) content in ER stores induced by beta -amyloid 1-42, suggesting that NCX3 was involved in the increase of ER Ca(2+) content stimulated by this peptide. By contrast, in the late phase (72 h), when the NCX3 proteolytic cleavage abruptly decreased, the occurrence of a parallel reduction in ER Ca(2+) content triggered ER stress, as revealed by caspase-12 activation. Concomitantly, the late increase in [Ca(2+)](i) coincided with neuronal death. Interestingly, NCX3 silencing caused an earlier activation of Aβ(1-42)-induced caspase-12. Indeed, in NCX3-silenced neurons, Aβ(1-42) exposure hastened caspase-dependent apoptosis, thus reinforcing neuronal cell death. These results suggest that Aβ(1-42), through Ca(2+)-dependent calpain activation, generates a hyperfunctional form of the Na+/Ca2+ exchanger NCX3 that, by increasing Ca(2+) content into ER, delays caspase-12 activation and thusER-stress and neuronal death.
2012
A new concept: Aβ1-42 generates a hyperfunctional proteolytic NCX3 fragment that delays caspase-12 activation and neuronal death / Pannaccione, Anna; Secondo, Agnese; Molinaro, Pasquale; D'Avanzo, C; Cantile, M; Esposito, A; Boscia, Francesca; Scorziello, Antonella; Sirabella, Rossana; Sokolow, S; Herchuelz, A; DI RENZO, GIANFRANCO MARIA LUIGI; Annunziato, Lucio. - In: THE JOURNAL OF NEUROSCIENCE. - ISSN 0270-6474. - 32:(2012), pp. 10609-10617. [10.1523/JNEUROSCI.5031-12.2012]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/507194
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 66
  • ???jsp.display-item.citation.isi??? 67
social impact