Effect of cysteamine on redox-sensitive thiol-containing proteins in the duodenal mucosa.

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.
Authors	Tetyana Khomenko, Xiaoming Deng, Martin R Jadus, Sandor Szabo
Journal	Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 309 Issue 4 Pg. 910-6 (Oct 03 2003) ISSN: 0006-291X [Print] United States
PMID	13679060 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References	DNA Primers DNA-Binding Proteins Early Growth Response Protein 1 Egr1 protein, rat Immediate-Early Proteins Sulfhydryl Compounds Transcription Factors Thioredoxins Cysteamine DNA DNA-(Apurinic or Apyrimidinic Site) Lyase
Topics	Animals Base Sequence Cysteamine (pharmacology) DNA (metabolism) DNA Primers DNA-(Apurinic or Apyrimidinic Site) Lyase (chemistry, metabolism) DNA-Binding Proteins (chemistry, metabolism) Duodenum (drug effects, metabolism) Early Growth Response Protein 1 Female Immediate-Early Proteins Intestinal Mucosa (drug effects, metabolism) Oxidation-Reduction Protein Binding Protein Transport Rats Rats, Sprague-Dawley Reverse Transcriptase Polymerase Chain Reaction Sulfhydryl Compounds (metabolism) Thioredoxins (chemistry, metabolism) Transcription Factors (chemistry, metabolism)

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