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Control of the Na+/Ca2+ exchanger 3 promoter by cyclic adenosine monophosphate and Ca2+ in differentiating neurons.
- Source :
-
Journal of neurochemistry [J Neurochem] 2003 Jan; Vol. 84 (2), pp. 282-93. - Publication Year :
- 2003
-
Abstract
- The human gene for member 3 of solute carrier family 8 (SLC8A3), encoding the Na+/Ca2+ exchanger isoform 3 (NCX3), was identified on chromosome 14q24.2. The minimal promoter region was predicted 250 bp upstream of exon 1. This was confirmed by luciferase reporter assays of pGL3-promoter constructs in transfected SH-SY5Y cells. The promoter activity was monitored during the differentiation of this cell line elicited by the sequential treatment with retinoic acid and brain-derived neurotrophic factor (BDNF). The activity was induced by cyclic AMP (cAMP) via the CRE (cAMP response element) and was stimulated by retinoic acid. The increase of intracellular Ca2+ induced by the partial depolarization of the plasma membrane with KCl down-regulated both the basal and the cAMP-stimulated transcription. The down-regulation of the latter may be mediated by the phosphorylation of the CRE-binding protein by a calmodulin-dependent kinase (CaMKII). The exposure of cells to BDNF after treatment with retinoic acid rapidly induced promoter activity during the initial five hours and phosphorylation of CRE-binding protein during the first two hours. The promoter activity was further enhanced by cAMP, but became insensitive to Ca2+. In BDNF-stimulated cells cAMP elevation caused the preferential phosphorylation of ATF1 instead of that of CRE-binding protein.
- Subjects :
- Activating Transcription Factors
Base Sequence
Blood Proteins metabolism
Brain-Derived Neurotrophic Factor pharmacology
Calcium pharmacology
Cell Differentiation drug effects
Cyclic AMP pharmacology
Cyclic AMP Response Element-Binding Protein metabolism
Down-Regulation drug effects
Down-Regulation physiology
Humans
Molecular Sequence Data
Neuroblastoma metabolism
Neurons cytology
Phosphorylation drug effects
Promoter Regions, Genetic drug effects
Sodium-Calcium Exchanger metabolism
Transcription Factors metabolism
Transfection
Tretinoin pharmacology
Tumor Cells, Cultured drug effects
Calcium metabolism
Cell Differentiation physiology
Cyclic AMP metabolism
Membrane Transport Proteins
Neurons metabolism
Promoter Regions, Genetic physiology
Sodium-Calcium Exchanger genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3042
- Volume :
- 84
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 12558991
- Full Text :
- https://doi.org/10.1046/j.1471-4159.2003.01511.x