K+-Dependent Na+/Ca2+ Exchanger Isoform 2, Nckx2, Takes Part in the Neuroprotection Elicited by Ischemic Preconditioning in Brain Ischemia.

Abstract

Sodium/Calcium exchangers are neuronal plasma membrane antiporters which, by coupling Ca2+ and Na+ fluxes across neuronal membranes, play a relevant role in brain ischemia. The most brain-expressed isoform among the members of the K+-dependent Na+/Ca2+ exchanger family, NCKX2, is involved in the progression of the ischemic lesion, since both its knocking-down and its knocking-out worsens ischemic damage. The aim of this study was to elucidate whether NCKX2 functions as an effector in the neuroprotection evoked by ischemic preconditioning. For this purpose, we investigated: (1) brain NCKX2 expression after preconditioning and preconditioning + ischemia; (2) the contribution of AKT and calpain to modulating NCKX2 expression during preconditioning; and (3) the effect of NCKX2 knocking-out on the neuroprotection mediated by ischemic preconditioning. Our results showed that NCKX2 expression increased in those brain regions protected by ischemic preconditioning. These changes were p-AKT-mediated since its inhibition prevented NCKX2 up-regulation. More interestingly, NCKX2 knocking-out significantly prevented the protection exerted by ischemic preconditioning. Overall, our results suggest that NCKX2 plays a fundamental role in the neuroprotective effect mediated by ischemic preconditioning and support the idea that the enhancement of its expression and activity might represent a reasonable strategy to reduce infarct extension after stroke.

• Authors: Ornella Cuomo, Rossana Sirabella, Francesca Boscia, Antonella Casamassa, Jonathan Lytton, Lucio Annunziato, Giuseppe Pignataro
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 13 (Jun 27 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 35806133 (Publication Type: Journal Article)

Chemical References

• Protein Isoforms
• Sodium-Calcium Exchanger
• Proto-Oncogene Proteins c-akt

Topics

• Brain Ischemia (genetics, metabolism)
• Humans
• Ischemic Preconditioning
• Neuroprotection
• Protein Isoforms (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Sodium-Calcium Exchanger (genetics, metabolism)