Functional Characterization of a Purified, Recombinant NF-κB/IκB Complex

Larson, Christopher J.; Li, Yian Wu; Mercurio, Frank; Müller, Rolf

doi:10.1006/bbrc.1999.0949

Cited by 2 publications

(1 citation statement)

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“…Dissociation of NF-κB from IκB is a critical step in NF-κB activation that leads to translocation of NF-κB to the nucleus, enabling DNA binding and transactivation (Gilmore, 1999;Hayden and Ghosh, 2004). The key event for NF-κB activation is phosphorylation of two serine residues at the N terminus of IκB (Ser 32 and Ser 36 for IkB-a) by IκB kinase (IKK) (Larson et al, 1999). To determine whether the effect of mGSTA4-4 modulated activation of NF-κB was through phosphorylation of IκB-α, we examined the expression of IκB-α and phosphor-IκB-α (p-IκB-α) in cytoplasmic fraction by Western blot analysis in the WT and VT/mGSTA4transfected MS1 cells (represented as one of three separate experiments).…”

Section: Mgsta4 Transfection Activates P-iκb-α Which Are Modulated Bymentioning

confidence: 99%

Endothelial glutathione-S-transferase A4-4 protects against oxidative stress and modulates iNOS expression through NF-κB translocation

Yang

Lick

et al. 2008

Toxicology and Applied Pharmacology

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Our recent work in endothelial cells and human atherosclerotic plaque showed that overexpression of glutathione-S-tranferases (GSTs) in endothelium protects against oxidative damage from aldehydes such as 4-HNE. Nuclear factor (NF)-kappaB plays a crucial role during inflammation and immune responses by regulating the expression of inducible genes such as inducible nitric oxide synthase (iNOS). 4-HNE induces apoptosis and affects NF-kappaB mediated gene expression, but conflicting results on 4-HNE's effect on NF-kappaB have been reported. We compared the effect of 4-HNE on iNOS and the NF-kappaB pathway in control mouse pancreatic islet endothelial (MS1) cells and those transfected with mGSTA4, a alpha-class GST with highest activity toward 4-HNE. When treated with 4-HNE, mGSTA4-transfected cells showed significant upregulation of iNOS and nitric oxide (NO) through (NF)-kappaB (p65) translocation in comparison with wild-type or vector-transfected cells. Immunohistochemical studies of early human plaques showed lower 4-HNE content and upregulation of iNOS, which we take to indicate that GSTA4-4 induction acts as an enzymatic defense against high levels of 4-HNE, since 4-HNE accumulated in more advanced plaques, when detoxification and exocytotic mechanisms are likely to be overwhelmed. These studies suggest that GSTA4-4 may play an important defensive role against atherogenesis through detoxification of 4-HNE and upregulation of iNOS.

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Section: Mgsta4 Transfection Activates P-iκb-α Which Are Modulated Bymentioning

confidence: 99%

Endothelial glutathione-S-transferase A4-4 protects against oxidative stress and modulates iNOS expression through NF-κB translocation

Yang

Lick

et al. 2008

Toxicology and Applied Pharmacology

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Reciprocal Effects of Toll-Like Receptors and miRNAs on Biological Processes in Human Health and Disease: A Systematic Review

2013

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The roles of miRNAs in human diseases are emerging. Manipulation of miRNA expression seems to be an effective approach to control disease severity. It has recently been found that Toll-like receptors and miRNAs work by exerting reciprocal effects. Toll-like receptor stimulation can lead to up-/down-regulation of various miRNA expressions. Lipopolysaccharide induction may result in interactions between different miRNAs. Several miRNAs are involved in cancers, indicating the importance of identifying strategies to properly manipulate their expression level. The control of various miRNA expression levels, taking into consideration the plethora of their target genes and the possibility that this may lead to contracting function, which is an important issue in treatment of any miRNA-based (phenotype) disease.

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Functional Characterization of a Purified, Recombinant NF-κB/IκB Complex

Cited by 2 publications

References 32 publications

Endothelial glutathione-S-transferase A4-4 protects against oxidative stress and modulates iNOS expression through NF-κB translocation

Endothelial glutathione-S-transferase A4-4 protects against oxidative stress and modulates iNOS expression through NF-κB translocation

Reciprocal Effects of Toll-Like Receptors and miRNAs on Biological Processes in Human Health and Disease: A Systematic Review

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