ERK1/2, p38, and JNK regulate the expression and the activity of the three isoforms of the Na+/Ca2+exchanger, NCX1, NCX2, and NCX3, in neuronal PC12 cells

Authors:
Open Access
Publisher website
Google Scholar
Abstract
J. Neurochem. (2012)122, 911–922. We evaluated whether changes in expression and activity of the three sodium/calcium exchanger isoforms, NCX1, NCX2, and NCX3 occurred in PC12 cells when the extracellular‐signal‐regulated kinases 1/2 (ERK1/2), c‐Jun N‐terminal kinases (JNK), and p38 mitogen‐activated protein kinases (MAPKs) were silenced, pharmacologically blocked, or activated with nerve growth factor (NGF). Several findings suggesting that MAPKs control NCX emerged: (1) A decrease in NCX1 and NCX3 basal expression occurred when JNK or MEK1, the extracellular‐signal‐regulated kinases 1/2 upstream activator, were pharmacologically blocked, respectively; (2) NGF increased cAMP response element‐binding 1 (CREB1) and Specificity Protein 1 (Sp1) binding to ncx1 promoter and CREB1 binding to two different sequences close to ncx2 transcription start site on genomic DNA; (3) An up‐regulation of NCX1 and NCX3, abrogated upon either MEK1 or p38 blockade, and a down‐regulation of NCX2, abolished upon p38 blockade, occurred upon NGF‐induced MAPK activation. The NCX1 up‐regulation was abolished upon either CREB1 or Sp1 silencing, whereas NCX2 down‐regulation was abrogated only by CREB1 silencing. The NCX3 up‐regulation was unaffected by CREB1 or Sp1 silencing and abolished upon proteasomal inhibition; (4) Whole‐cell Na+/Ca2+exchange decreased when MEK1 and JNK were blocked and increased when MAPKs were activated by NGF. Collectively, these results demonstrate a MAPK‐dependent regulation of NCX expression and activity which could be relevant in mediating some of the effects of MAPKs in neurons.

This publication has 40 references indexed in Scilit: