PMID- 21293012
OWN - NLM
STAT- MEDLINE
DCOM- 20110419
LR  - 20161122
IS  - 1524-4628 (Electronic)
IS  - 0039-2499 (Linking)
VI  - 42
IP  - 3
DP  - 2011 Mar
TI  - NCX1 is a novel target gene for hypoxia-inducible factor-1 in ischemic brain 
      preconditioning.
PG  - 754-63
LID - 10.1161/STROKEAHA.110.597583 [doi]
AB  - BACKGROUND AND PURPOSE: The sodium-calcium exchanger-1 (NCX1) represents a key 
      mediator for maintaining [Na(+)](i) and [Ca(2+)](i) homeostasis. Although changes 
      in NCX1 protein and transcript expression have been detected during stroke, its 
      transcriptional regulation is still unknown. Thus far, however, there is evidence 
      that hypoxia-inducible factor-1 (HIF-1) is a nuclear factor required for 
      transcriptional activation of several genes implicated in stroke. The main 
      objective of this study was to investigate whether NCX1 gene might be a novel 
      target of HIF-1 in the brain. METHODS: Here we report that: (1) in neuronal 
      cells, NCX1 increased expression after oxygen and glucose deprivation or 
      cobalt-induced HIF-1 activation was prevented by silencing HIF-1; (2) the brain 
      NCX1 promoter cloned upstream of the firefly-luciferase gene contained 2 regions 
      of HIF-1 target genes called hypoxia-responsive elements that are sensitive to 
      oxygen and glucose deprivation or cobalt chloride; (3) HIF-1 specifically bound 
      hypoxia-responsive elements on brain NCX1, as demonstrated by band-shift and 
      chromatin immunoprecipitation assays; (4) HIF-1alpha silencing prevented NCX1 
      upregulation and neuroprotection induced by ischemic preconditioning; and (5) 
      NCX1 silencing partially reverted the preconditioning-induced neuroprotection in 
      rats. CONCLUSIONS: NCX1 gene is a novel HIF-1 target, and HIF-1 exerts its 
      prosurvival role through NCX1 upregulation during brain preconditioning.
FAU - Valsecchi, Valeria
AU  - Valsecchi V
AD  - Division of Pharmacology, Department of Neuroscience, School of Medicine, 
      "Federico II" University of Naples, Via S. Pansini 5, 80131 Naples, Italy.
FAU - Pignataro, Giuseppe
AU  - Pignataro G
FAU - Del Prete, Annalisa
AU  - Del Prete A
FAU - Sirabella, Rossana
AU  - Sirabella R
FAU - Matrone, Carmela
AU  - Matrone C
FAU - Boscia, Francesca
AU  - Boscia F
FAU - Scorziello, Antonella
AU  - Scorziello A
FAU - Sisalli, Maria Jose
AU  - Sisalli MJ
FAU - Esposito, Elga
AU  - Esposito E
FAU - Zambrano, Nicola
AU  - Zambrano N
FAU - Di Renzo, Gianfranco
AU  - Di Renzo G
FAU - Annunziato, Lucio
AU  - Annunziato L
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110203
PL  - United States
TA  - Stroke
JT  - Stroke
JID - 0235266
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Sodium-Calcium Exchanger)
RN  - 0 (sodium-calcium exchanger 1)
SB  - IM
MH  - Animals
MH  - Brain/*blood supply/*metabolism
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Gene Targeting/*methods
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*physiology
MH  - Ischemic Attack, Transient/genetics/metabolism
MH  - Ischemic Preconditioning/*methods
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Rats, Wistar
MH  - Sodium-Calcium Exchanger/biosynthesis/genetics/*metabolism
EDAT- 2011/02/05 06:00
MHDA- 2011/04/20 06:00
CRDT- 2011/02/05 06:00
PHST- 2011/02/05 06:00 [entrez]
PHST- 2011/02/05 06:00 [pubmed]
PHST- 2011/04/20 06:00 [medline]
AID - STROKEAHA.110.597583 [pii]
AID - 10.1161/STROKEAHA.110.597583 [doi]
PST - ppublish
SO  - Stroke. 2011 Mar;42(3):754-63. doi: 10.1161/STROKEAHA.110.597583. Epub 2011 Feb 
      3.