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Deferoxamine synergistically enhances iron-mediated AP-1 activation: a showcase of the interplay between extracellular-signal-regulated kinase and tyrosine phosphatase.
- Source :
-
Free radical research [Free Radic Res] 2007 Oct; Vol. 41 (10), pp. 1135-42. - Publication Year :
- 2007
-
Abstract
- Deferoxamine (DFO) is a drug widely used for iron overload treatment to reduce body iron burden. In the present study, it was shown in mouse epidermal JB6 cells that all iron compounds transiently induced extracellular signal-regulated kinases (ERK) phosphorylation, whereas DFO further enhanced ERK phosphorylation over long periods. The ERK phosphorylation by DFO treatment appears to be due to the inhibition of MAPK phosphatases (MKP) by DFO. The combined effects of iron-initiated MAPK activation and DFO-mediated MKP inhibition resulted in a synergistic enhancement on AP-1 activities. The results indicate that the interplay between MAPK and MKP is important in regulating the extent of AP-1 activation. It is known that administration of DFO in iron overload patients often results in allergic responses at the injection sites. The results suggest that this synergistic AP-1 activation might play a role in DFO-induced skin immune responses of iron overload patients.
- Subjects :
- Animals
Cell Line
Immune System
Iron chemistry
Iron metabolism
Mice
Models, Biological
NFATC Transcription Factors metabolism
Phosphorylation
Siderophores pharmacology
Skin immunology
Tyrosine chemistry
Deferoxamine pharmacology
Mitogen-Activated Protein Kinase 3 metabolism
Protein Tyrosine Phosphatases metabolism
Transcription Factor AP-1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1071-5762
- Volume :
- 41
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Free radical research
- Publication Type :
- Academic Journal
- Accession number :
- 17886035
- Full Text :
- https://doi.org/10.1080/10715760701609061