scholarly journals Interaction of mitochondrial thioredoxin with glucocorticoid receptor and NF-κB modulates glucocorticoid receptor and NF-κB signalling in HEK-293 cells

2009 ◽  
Vol 422 (3) ◽  
pp. 521-531 ◽  
Author(s):  
Anna-Maria G. Psarra ◽  
Stefan Hermann ◽  
George Panayotou ◽  
Giannis Spyrou
Keyword(s):  
Transcription Factors ◽  
Glucocorticoid Receptor ◽  
Nuclear Factor Κb ◽  
Reduced Form ◽  
Mrna Levels ◽  
Cytochrome Oxidase Subunit ◽  
Hek 293 ◽  
293 Cells ◽  
Factor Α ◽  
Necrosis Factor

Trx2 (mitochondrial thioredoxin) is an antioxidant and anti-apoptotic 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-κB (nuclear factor κB). 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-κB 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-κB 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-κB reporter genes. Moreover, Trx2 overexpression modulates the mRNA levels of the COX1 (cytochrome oxidase subunit I) and Cytb (cytochrome b), which are known to be regulated by GR and NF-κB. Increased expression of Trx2 differentially affects the expression of Cytb. The glucocorticoid dexamethasone potentiates the expression of Cytb, whereas TNFα (tumour necrosis factor α) down-regulates it. These results suggest a regulatory role for Trx2 in GR and NF-κB signalling pathways.

scholarly journals Regulation of hypoxia-inducible factor-1α by NF-κB

2008 ◽  
Vol 412 (3) ◽  
pp. 477-484 ◽  
Author(s):  
Patrick van Uden ◽  
Niall S. Kenneth ◽  
Sonia Rocha
Keyword(s):  
Hypoxia Inducible Factor ◽  
Nuclear Factor Κb ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Low Oxygen ◽  
Prolyl Hydroxylases ◽  
Hypoxic Conditions ◽  
Factor Α ◽  
Interfering Rna ◽  
Necrosis Factor

HIF (hypoxia-inducible factor) is the main transcription factor activated by low oxygen tensions. HIF-1α (and other α subunits) is tightly controlled mostly at the protein level, through the concerted action of a class of enzymes called PHDs (prolyl hydroxylases) 1, 2 and 3. Most of the knowledge of HIF derives from studies following hypoxic stress; however, HIF-1α stabilization is also found in non-hypoxic conditions through an unknown mechanism. In the present study, we demonstrate that NF-κB (nuclear factor κB) is a direct modulator of HIF-1α expression. The HIF-1α promoter is responsive to selective NF-κB subunits. siRNA (small interfering RNA) studies for individual NF-κB members revealed differential effects on HIF-1α mRNA levels, indicating that NF-κB can regulate basal HIF-1α expression. Finally, when endogenous NF-κB is induced by TNFα (tumour necrosis factor α) treatment, HIF-1α levels also change in an NF-κB-dependent manner. In conclusion, we find that NF-κB can regulate basal TNFα and, in certain circumstances, the hypoxia-induced HIF-1α.

scholarly journals Tumour necrosis factor α induces co-ordinated activation of rat GSH synthetic enzymes via nuclear factor κB and activator protein-1

2005 ◽  
Vol 391 (2) ◽  
pp. 399-408 ◽  
Author(s):  
Heping Yang ◽  
Nathaniel Magilnick ◽  
Xiaopeng Ou ◽  
Shelly C. Lu
Keyword(s):  
Promoter Activity ◽  
Nuclear Factor Κb ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Activator Protein 1 ◽  
Tumour Necrosis Factor Α ◽  
Synthetic Enzymes ◽  
H4iie Cells ◽  
Factor Α ◽  
Necrosis Factor

GSH synthesis occurs via two enzymatic steps catalysed by GCL [glutamate–cysteine ligase, made up of GCLC (GCL catalytic subunit), and GCLM (GCL modifier subunit)] and GSS (GSH synthetase). Co-ordinated up-regulation of GCL and GSS further enhances GSH synthetic capacity. The present study examined whether TNFα (tumour necrosis factor α) influences the expression of rat GSH synthetic enzymes. To facilitate transcriptional studies of the rat GCLM, we cloned its 1.8 kb 5′-flanking region. TNFα induces the expression and recombinant promoter activities of GCLC, GCLM and GSS in H4IIE cells. TNFα induces NF-κB (nuclear factor κB) and AP-1 (activator protein 1) nuclear-binding activities. Blocking AP-1 with dominant negative c-Jun or NF-κB with IκBSR (IκB super-repressor, where IκB stands for inhibitory κB) lowered basal expression and inhibited the TNFα-mediated increase in mRNA levels of all three genes. While all three genes have multiple AP-1-binding sites, only GCLC has a NF-κB-binding site. Overexpression with p50 or p65 increased c-Jun mRNA levels, c-Jun-dependent promoter activity and the promoter activity of GCLM and GSS. Blocking NF-κB also lowered basal c-Jun expression and blunted the TNFα-mediated increase in c-Jun mRNA levels. TNFα treatment resulted in increased c-Jun and Nrf2 (nuclear factor erythroid 2-related factor 2) nuclear binding to the antioxidant response element of the rat GCLM and if this was prevented, TNFα no longer induced the GCLM promoter activity. In conclusion, both c-Jun and NF-κB are required for basal and TNFα-mediated induction of GSH synthetic enzymes in H4IIE cells. While NF-κB may exert a direct effect on the GCLC promoter, it induces the GCLM and GSS promoters indirectly via c-Jun.

Mutant p53 Enhances Nuclear Factor κB Activation by Tumor Necrosis Factor α in Cancer Cells

2007 ◽  
Vol 67 (6) ◽  
pp. 2396-2401 ◽  
Author(s):  
Lilach Weisz ◽  
Alexander Damalas ◽  
Michalis Liontos ◽  
Panagiotis Karakaidos ◽  
Giulia Fontemaggi ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Cancer Cells ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Nuclear Factor Κb ◽  
Mutant P53 ◽  
Nuclear Factor ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Alimentary induced fatty liver and adjuvant therapy with effective natural bioactive molecules

2011 ◽  
Vol 152 (26) ◽  
pp. 1035-1042 ◽  
Author(s):  
Viktor Hegedüs ◽  
Domokos Gerő ◽  
Zoltán Mihály ◽  
Attila Szijártó ◽  
Tivadar Zelles ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Fatty Liver ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Redox Homeostasis ◽  
Mrna Levels ◽  
Factor Α ◽  
Oxide Synthase ◽  
Necrosis Factor ◽  
Inducible Nitric Oxide

Changes of redox-homeostasis generate cytokines, and free radicals influence many intracellular signaling pathways in different liver diseases. Liophylised table beet and carrot powder (GPS Powder Kft. 1361/004/2003BFÁÉÉÁ) containing bioactive components such as betaine, betanins, betaxanthins, flavonoids, polyphenols, glutamine, beta carotene, vitamins and folic acid may produce changes various cellular pathways. Aim: The aim of this study was to determine the protecting effects of bioactive agents of the liophylised table beet and carrot powder on fatty liver in a “short term” experiment. Method: Male Wistar rats were fed with chow with or without high fat (2% cholesterol, 0.5% cholic acid, 20% sunflower oil) and treated with 0.1 or 1 g/bwkg/day natural product for ten days parallel with the feedings. Cyclooxygenase-2, inducible nitric oxide synthase and tumor necrosis factor-α mRNA levels were determined using molecular biologic methods. Free radicals, H-donating activity, reducing power and free SH-group concentrations were determined by luminometry and spectrophotometry. Mobilized methyl groups were assayed by over pressure liquid chromatography method in liver homogenates. Results: It was found that the higher dose of the natural product better decreased the induced free radical reactions, cyclooxygenase-2, inducible nitric oxide synthase and tumor necrosis factor-α mRNA-levels both in normal and fatty liver tissues. Although treatments failed to exert significant changes in all global antioxidant parameters, mobilized methyl group concentrations were higher after treatments in fatty liver. Favorable tendencies were also noted in the redox-homeostasis of the fatty liver after treatment. Conclusions: As expected, lyophylised table beet and carrot proved to be a “functional food” in rats with alimentary fat induced fatty liver. It cannot be ruled out that this beneficial effect may have clinical relevance. Orv. Hetil., 2011, 152, 1035–1042.

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