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Effect of cysteamine on redox-sensitive thiol-containing proteins in the duodenal mucosa.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2003 Oct 03; Vol. 309 (4), pp. 910-6. - Publication Year :
- 2003
-
Abstract
- Recent studies from our laboratory demonstrated that Egr-1 is upregulated in the rat duodenal mucosa during cysteamine-induced duodenal ulceration and that antisense egr-1 oligonucleotide aggravates the duodenal ulcers. This study was aimed to determine the effects of cysteamine on redox-sensitive Egr-1 transcriptional activity and on other thiol-containing proteins such as redox factor-1 (Ref-1) and thioredoxin (Trx). Here we demonstrate for the first time that cysteamine increases the expression and nuclear translocation of Egr-1, Ref-1, and Trx, and activates binding of Egr-1 to DNA. Moreover, we also show that Egr-1 forms a complex with other redox-sensitive transcription factors (e.g., AP-1, AP-2, NFATc, Sp1, PAX-5, MTF-1, c-Myb, and CREB) in rat duodenal mucosa and that cysteamine enhances the formation of these complexes. The antioxidant ebselen markedly elevated the nuclear Ref-1 expression and Egr-1/DNA binding, and decreased the ulcerogenic effect of cysteamine as did catalase. Thus, redox-sensitive signaling systems seem to play an important role in cysteamine-induced duodenal ulceration.
- Subjects :
- Animals
Base Sequence
DNA metabolism
DNA Primers
DNA-(Apurinic or Apyrimidinic Site) Lyase chemistry
DNA-Binding Proteins chemistry
Duodenum metabolism
Early Growth Response Protein 1
Female
Intestinal Mucosa metabolism
Oxidation-Reduction
Protein Binding
Protein Transport
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Thioredoxins chemistry
Transcription Factors chemistry
Cysteamine pharmacology
DNA-(Apurinic or Apyrimidinic Site) Lyase metabolism
DNA-Binding Proteins metabolism
Duodenum drug effects
Immediate-Early Proteins
Intestinal Mucosa drug effects
Sulfhydryl Compounds metabolism
Thioredoxins metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 309
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 13679060
- Full Text :
- https://doi.org/10.1016/j.bbrc.2003.08.092