Title: Deferoxamine synergistically enhances iron-mediated AP-1 activation: a showcase of the interplay between extracellular-signal-regulated kinase and tyrosine phosphatase.
Authors: Huang, Xi; Dai, Jisen; Huang, Chuanshu; Zhang, Qi; Bhanot, Opinder; Pelle, Edward
Published In Free Radic Res, (2007 Oct)
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.
PubMed ID: 17886035
MeSH Terms: Animals; Cell Line; Deferoxamine/pharmacology*; Immune System; Iron/chemistry; Iron/metabolism; Mice; Mitogen-Activated Protein Kinase 3/metabolism*; Models, Biological; NFATC Transcription Factors/metabolism; Phosphorylation; Protein Tyrosine Phosphatases/metabolism*; Siderophores/pharmacology; Skin/immunology; Transcription Factor AP-1/metabolism*; Tyrosine/chemistry