Interaction of mitochondrial thioredoxin with glucocorticoid receptor and NF-kappaBeta modulates glucocorticoid receptor and NF-kappaB signaling in HEK 293 cells. The Biochemical journal [Biochem J] Journal article

Mitochondrial thioredoxin (Trx2) is an antioxidant, antiapoptotic factor, essential for cell viability. The cytoplasmic thioredoxin (Trx1) is a cofactor and regulator of redox sensitive transcription factors such as the glucocorticoid receptor (GR) and NF-kappaB. Both transcription factors have been detected in mitochondria and a role in mitochondrial transcription regulation and apoptosis has been proposed. Here, we show using surface plasmon resonance and immunoprecepitation that GR and the p65 subunit of NF-kappaBeta 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-kappaB can interact with Trx2 in the oxidized, but not the reduced form. Using HEK 293 cell lines with increased or decreased expression of Trx2, we show that Trx2 modulates transcription of GR and NF-kappaB reporter genes. Moreover, Trx2 overexpression modulates the mRNA levels of the mitochondrial COX I, and Cyt b, whose expression is known to be regulated by GR and NF-kappaB. Increased expression of Trx2 differentially affects the expression of Cyt b. The glucocorticoid dexamethasone potentiates the expression of Cyt b, whereas TNFalpha downregulates it. These results suggest a regulatory role for Trx2 in GR and NF-kappaB signalling pathways.

The Biochemical journal [Biochem J]