Journal
BIOCHEMICAL JOURNAL
Volume 422, Issue -, Pages 521-531Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BJ20090107
Keywords
glucocorticoid receptor (GR); mitochondria; nuclear factor kappa B (NF-kappa B); reactive oxygen species (ROS); thioredoxin; transcription
Categories
Funding
- Biomedical Research Foundation of the Academy of Athens
- European Community Translational and Functional Onco-Genomics project [503438]
Ask authors/readers for more resources
Trx2 (mitochondrial thioredoxin) is an antioxidant and antiapoptotic factor essential for cell viability. Trx1 (cytoplasmic thioredoxin) is a co-factor and regulator of redox-sensitive transcription factors such as the GR (glucocorticoid receptor) and NF-kappa B (nuclear factor kappa B). Both transcription factors have been detected in mitochondria and a role in mitochondrial transcription regulation and apoptosis has been proposed. In the present study, we show using SPR (Surface plasmon resonance) and immunoprecepitation that GR and the p65 subunit of NF-kappa B are Trx2-interacting proteins. The interaction of Trx2 with GR is independent of the presence of GR ligand and of redox conditions. The p65 subunit of NF-kappa B can interact with Trx2 in the oxidized, but not the reduced, form. Using HEK (human embryonic kidney)-293 cell lines with increased or decreased expression of Trx2, we show that Trx2 modulates transcription of GR and NF-kappa B reporter genes. Moreover, Trx2 overexpression modulates the rnRNA levels of the COX1 (cytochrome oxidase subunit 1) and Cytb (cytochrome b), which are known to be regulated by GR and NF-kappa B. Increased expression of Trx2 differentially affects the expression of Cytb. The glucocorticoid dexamethasone potentiates the expression of Cytb, whereas TNF alpha (tumour necrosis factor alpha) down-regulates it. These results suggest a regulatory role for Trx2 in GR and NF-kappa B signalling pathways.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available