What genes does NF-kB regulate?
NF-κB regulates the expression of a large array of genes involved in different aspects of atherosclerotic pathogenesis. In vascular endothelial cells, NF-κB mediates induction of pro-inflammatory cytokines, chemotactic factors and adhesion molecules, thereby promoting monocyte recruitment and disease progression.
What activates NF-kB?
The primary mechanism for canonical NF-κB activation is the inducible degradation of IκBα triggered through its site-specific phosphorylation by a multi-subunit IκB kinase (IKK) complex. IKK can be activated by different stimuli, including cytokines, growth factors, mitogens, microbial components and stress agents.
What does IkB do to NF-kB?
The best-studied and major IkB protein is IkBa. The IkBs bind to NF-kB dimers and sterically block the function of their NLSs, thereby causing their cytoplasmic retention. In order to get NF-kB into the nucleus, its site of action, the cytoplasmic NF-kB:IkB complex needs to be disrupted.
What is NF-kB inflammation?
Nuclear factor-κB (NF-κB), a transcription factor that is essential for inflammatory responses, is one of the most important molecules linking chronic inflammation to cancer, and its activity is tightly regulated by several mechanisms.
How does NF kB induce gene expression?
Activation of the NF-κB is initiated by the signal-induced degradation of IκB proteins. With the degradation of IκB, the NF-κB complex is then freed to enter the nucleus where it can ‘turn on’ the expression of specific genes that have DNA-binding sites for NF-κB nearby.
How is NF kB regulated?
It is regulated through phosphorylation of p100 by the IKKα subunit of the IKK complex, which results in ubiquitination and subsequent partial degradation of p100 by the proteasome, releasing transcriptionally active p50/RelB complexes (Senftleben et al.
How is NF-kB regulated?
Where is NF-kB found?
While in an inactivated state, NF-κB is located in the cytosol complexed with the inhibitory protein IκBα. Through the intermediacy of integral membrane receptors, a variety of extracellular signals can activate the enzyme IκB kinase (IKK).
How is NF-kB measured?
Another common method to measure NF-κB activity at the transcriptional activation level is to use a gene reporter assay, which introduces an exogenous NF-κB consensus promoter sequence linked to a measurable ‘reporter gene’ such as luciferase (18).
What is NF kB activity?
NF-κB (nuclear factor kappa light chain enhancer of activated B cells) is a family of highly conserved transcription factors that regulate many important cellular behaviours, in particular, inflammatory responses, cellular growth and apoptosis. NF-κB is also involved in diseases such as cancer, arthritis and asthma.
How do you reduce NF kB?
Antioxidants such as PDTC40 and NAC41 have shown a potential to inhibit NF-κB activation either by exogeneous induction (e.g. LPS, TNFα) or hydrogen peroxide treatment. Antioxidants are likely to inhibit NF-κB by scavenging reactive oxygen intermediates involved in the NF-κB pathway42.
How do you measure NF-kB activation?