A requirement for thioredoxin in redox-sensitive modulation of T-cadherin expression in endothelial cells
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID 1196446
Author(s) Joshi, Manjunath B; Ivanov, Danila; Philippova, Maria; Kyriakakis, Emmanouil; Erne, Paul; Resink, Thérèse J
Author(s) at UniBasel Erne, Paul
Resink, Thérèse J.
Year 2008
Title A requirement for thioredoxin in redox-sensitive modulation of T-cadherin expression in endothelial cells
Journal Biochemical journal
Volume 416
Number 2
Pages / Article-Number 271-80
Keywords endothelial cell, oxidative stress, T-cadherin, thioredoxin, transcriptional regulation
Abstract T-cad (T-cadherin), a glycosylphosphatidylinositol-anchored cadherin superfamily member, is expressed widely in the brain and cardiovascular system, and absent, decreased, or even increased, in cancers. Mechanisms controlling T-cad expression are poorly understood. The present study investigated transcriptional regulation of T-cad in ECs (endothelial cells). Conditions of oxidative stress (serum-deprivation or presence of H(2)O(2)) elevate T-cad mRNA and protein levels in ECs. Reporter gene analysis, using serially deleted T-cad promoter stretches ranging from -99 to -2304 bp, located the minimal promoter region of T-cad within -285 bp from the translation start site. Reporter activity in ECs transfected with the -285 bp construct increased under conditions of oxidative stress, and this was normalized by antioxidant N-acetylcysteine. An electrophoretic-mobility-shift assay revealed a specific nucleoprotein complex unique to -156 to -203 bp, which increased when nuclear extracts from oxidatively stressed ECs were used, suggesting the presence of redox-sensitive binding element(s). MS analysis of the nucleoprotein complex unique to -156 to -203 bp after streptavidin-agarose pull-down detected the presence of the redox-active protein thioredoxin. The presence of thioredoxin-1 in a nuclear extract from oxidatively stressed ECs was demonstrated after immunoprecipitation and immunoblotting. Transfection of ECs with thioredoxin-1 small interfering RNA abrogated oxidative-stress-induced up-regulation of T-cad transcripts and protein. We conclude that thioredoxin-1 is an important determinant of redox-sensitive transcriptional up-regulation of T-cad in ECs.
Publisher Portland Press
ISSN/ISBN 0264-6021
edoc-URL http://edoc.unibas.ch/dok/A6006615
Full Text on edoc No
Digital Object Identifier DOI 10.1042/BJ20080765
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/18627351
ISI-Number WOS:000261346300012
Document type (ISI) Article

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