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Elevated intracellular calcium increases ferritin H expression through an NFAT-independent post-transcriptional mechanism involving mRNA stabilization
- Source :
- Biochemical Journal. 411:107-113
- Publication Year :
- 2008
- Publisher :
- Portland Press Ltd., 2008.
-
Abstract
- An increase in intracellular Ca2+ is one of the initiating events in T-cell activation. A calcium-mediated signalling cascade in T-cells involves activation of calcineurin and the dephosphorylation and translocation of NFAT (nuclear factor of activated T-cells), resulting in the transcriptional activation of target genes such as IL-2 (interleukin-2). In the present study, we found that increased intracellular calcium leads to induction of the antioxidant protein ferritin H. We previously reported that the ferritin H gene is transcriptionally activated under oxidative stress conditions through an ARE (antioxidant-responsive element). The facts that the ferritin H ARE contains a composite AP-1 (activator protein 1) site and that NFAT collaborates with AP-1 transcription factors led us to test whether calcium-activated NFAT is involved in the ferritin H induction through the ARE. Treatment of Jurkat T-cells with the calcium ionophore, ionomycin, increased ferritin H mRNA and protein expression. Although NFAT translocated to the nucleus and bound a consensus NFAT sequence located in the IL-2 promoter after ionomycin treatment, it did not activate ferritin H transcription despite the presence of a putative NFAT-binding sequence in the ferritin H ARE. In addition, the calcineurin inhibitor cyclosporin A treatment blocked ionomycin-mediated NFAT nuclear translocation but failed to abrogate the increase in ferritin H mRNA. Analysis of mRNA stability after actinomycin D treatment revealed that ionomycin prolongs ferritin H mRNA half-life. Taken together, these results suggest that ionomycin-mediated induction of ferritin H may occur in an NFAT-independent manner but through post-transcriptional stabilization of the ferritin H mRNA.
- Subjects :
- RNA Stability
Response Elements
Biochemistry
Article
Calcium in biology
Jurkat Cells
Mice
chemistry.chemical_compound
Cyclosporin a
Animals
Humans
Molecular Biology
Transcription factor
NFATC Transcription Factors
biology
Calcineurin
Ionomycin
NFAT
3T3 Cells
Cell Biology
MRNA stabilization
Molecular biology
Ferritin
Gene Expression Regulation
chemistry
Apoferritins
biology.protein
Calcium
Subjects
Details
- ISSN :
- 14708728 and 02646021
- Volume :
- 411
- Database :
- OpenAIRE
- Journal :
- Biochemical Journal
- Accession number :
- edsair.doi.dedup.....a0f2d5a1a1a7486113db5c53e997c75c