Redox sensitive transcriptional

It is possible that dietary flavonoids participate in the regulation of cellular function independent of their antioxidant properties. Other non-antioxidant direct effects reported include inhibition of prooxidant enzymes (xanthine oxidase, NAD(P)H oxidase, lipoxygenases), induction of antioxidant enzymes (superoxide dismutase, gluthathione peroxidase, glutathione S-transferase), and inhibition of redox-sensitive transcription factors. 

As already mentioned, van Kuijk and colleagues (Kalariya et al., 2008) tested the effects of oxidation products of [i-carotcnc, lutein, and zeaxanthin on the activation of redox-sensitive transcription factors, NF-kB, and AP-1 in cultured ARPE-19 cells. Degradation products of all three carotenoids induced activation of NF-kB and AP-1, and these effects were ameliorated by pretreatment of cells with 1 mM NAC. NF-kB is a major transcription factor that binds to promoter sites of many pro-inflammatory cytokines such as IL-1, IL-6, TNF-a, and iNOS. These results indicate that the degradation products of carotenoids can stimulate a pro-inflammatory pathway. 

In summary, the apparent redox modulation of lycopene certainly affects two important redox sensitive transcription factors at higher concentrations of lycopene. However, electrophilic lycopene oxidation products cannot be ruled out as the major activators and the activation may be due to specific molecular interactions. 

Micromolar quantities of RNS are generated primarily by nitric oxide synthase 2 (NOS2), an enzyme that is up-regulated during colon-cancer progression. As discussed below, deoxycholate (DOC), a hydrophobic secondary bile acid, activates the redox-sensitive transcription factor NF-kB, resulting in increased levels of NOS2 and enhanced S-nitrosylation of proteins. Additional sources of bile-acid-induced ROS and RNS are also likely. ... 

The transcription of nir and nor genes in P. stutzeri (Cuypers and Zumft, 1992, 1993) and P. aeruginosa (Zimmermann et al., 1991) would appear to be controlled in part by homologs of the Fnr protein of E. coli (Guest, 1992) which is a redox sensitive, transcriptional activator. Fnr boxes (binding sequences) are located upstream from norC, nirM and nirS. It is likely therefore that Fnr-like proteins participate in a regulatory mechanism which derepresses the synthesis... 

It now seems that an overdose of paracetamol causes a massive chemical stress, which causes an immediate adaptive defense response in the liver cell, which senses danger via redox-sensitive transcription factors. A number of mechanisms are involved, including the release, as a result of the stress, of a transcription factor Nrf-2 from its binding with Keap 1, a cytoplasmic inhibitor. Nrf-2 translocates to the nucleus and with other activators binds to an antioxidant-response element. This leads to transcription of a number of genes, so producing a... 

Luster MI, Simeonova PP. 1998. Asbestos induces inflammatory cytokines in the lung through redox sensitive transcription factors. Toxicol Lett 102-103 271-275. 

Moreover GSH concentration indirectly controls a host of redox-sensitive transcription factors such as NF-kB and AP-1, modulates the genes for pro-inflammatory mediators as well as protective antioxidant genes such as y-GCS, Mn-superoxide dismutase, and heme oxygenase-1. Also TNF-a, p38 MAP kinase activation and p38 MAP kinase-mediated RANTES (regulated upon activation, normal T-cells expressed and secreted ) production is redox regulated [24]. The role of RANTES in the inflammatory and allergic response has been recently elucidated [25], indicating a role of intracellular GSH also in this particular field of inflammation. 

Rensing H, Jaeschke H, Bauer 1, Patau C, Datene V, Pannen BH and Bauer M, Differential activation pattern of redox-sensitive transcription factors and stress-inducible dilator systems heme oxygenase-1 and inducible nitric oxide synthase in hemorrhagic and endotoxic shock. Cril Care Med 29(10) 1962-71,2001. 

Since an extreme pro-oxidant status of a cell can lead to a progressive loss of cellular function and eventual death, cells have developed mechanisms to detect changes in the redox status of cells. These switches are used to regulate and turn on the antioxidant machinery of the cell. These signals are largely mediated by redox-sensitive transcription factors. Although a large number of very extensively studied transcription factors are now know to respond to redox status, nuclear factor-kappaB (NF-kB) deserves special mention. NF-kB usually resides in the... 

Kim, E.H., Surh, Y.J. 2006. 15-deoxy-Deltal2,14-prostaglandin J2 as a potential endogenous regulator of redox-sensitive transcription factors. Biochem. Pharmacol. 72 1516-1528. 

Of the redox-sensitive transcription factors USFl/2, AP-1 and ARE binding proteins have been implicated in the transcriptional activation of both the MT-1 and HO-1 genes induced by heme-hemopexin [112]. Several lines of evidence demonstrate a particular role for the MRE-binding protein, MTF-1, in cellular oxidative stress leading to MT induction. The MRE responds to H2O2 however, high concentrations of H2O2, at least 500 pM, are required [133, 134]. Certainly, DNA... 

The activation of nuclear transcription factors has been shown to be necessary for the mechanism by which oxLDLs increase the expression of genes involved in the cell growth, differentiation, and prolifraative responses observed in atherosclerosis. In fact, it has been demonstrated that oxLDLs stimulate activator protein-1 (AP-1) DNA-binding activity in fibroblasts, SMCs, and ECs, possibly via JNKs and ERKs, and that lipid peroxidation products participates in this phenomenon. The stimulation of DNA-binding activity of another redox-sensitive transcription factor, nuclear factor k B (NF-kB), by oxLDL has also been described. ... 

A marked activation of AP-1 nuclear binding as induced by 1-10 pM 4-HNE, has now been demonstrated in different cytotypes including murine and human macrophageshuman hepatic stellate cells, and rat hepatocytes. With regard to another well-studied redox-sensitive transcription factor, NF-kB, 4-HNE does not appear to influence its activation and nuclear translocation in the mentioned cyto-types. Moreover, in nemoblastoma-derived PC 12 cell line, 4-HNE activates AP-1 and significantly downregulates NF-kB nuclear binding. ... 

Nuclear factor E2-related factor 2 (Nrf2) is a basic leucine zipper redox-sensitive transcription factor that controls the basal and inducible expression of a battery of antioxidant genes. It induces expression and upregulation of cytoprotective and antioxidant/detoxifying genes that attenuate tissue injury (Lee and Johnson, 2004). Under physiological conditions, NrF2 is localized in the cytoplasm where it binds... 

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