Nuclear factor inhibitor

Renin-Angiotensin-Aldosterone System ACE Inhibitors Nuclear Factor-icB... 

Higuchi, M., Singh, S., Chan, H., and Aggarwal, B. B., 1995, Protease inhibitors differentially regulate tumor necrosis factor-induced apoptosis, nuclear factor -kB activation, cytotoxicity, and differentiation. Blood 86 2248-2256. 

After damage or infection, monocytes and KCs in the area detect the damaged cells or infectious agent and respond with release of primary mediators such as TNFa, IL-1 and some IL-6. These cytokines activate the surrounding cells, that respond with a secondary, amplified release of cytokines. This second wave includes large amounts of IL-6, which induce the synthesis of acute phase proteins in hepatocytes and chemoattractants such as IL-8 and MCP-1. These events will then lead to the typical inflammatory reactions. Both IL-1 and TNFa activate the central regulatory protein of many reactions involved in immunity and inflammation, nuclear factor kappa B (NFkB). These cytokines cause dissociation of NFkB from its inhibitor IkB, which makes translocation of NFkB to the nucleus possible. In the nucleus active NFkB induces the transcription of the second wave cytokines (see also Chapter 7 for the molecular mechanisms of cytokine-mediated cell activation). 

Although very few terrestrial plant alkaloids contain halogen, brominated alkaloids have been reported from the marine environment. From the Okinawan marine sponge Hymemacidon sp., several bromopyrrole alkaloids have been described, e.g., tauroacidins A and B, Fig. (35) [262], konbuacidin A, Fig. (36) [263] and spongiacidins A-D [264]. Several species of sponges contain hymenialdisine, Fig. (37), which has been shown as a potent inhibitor of nuclear factor kappa B and interleukin-8 production in vitro [265,266]. 

Wang W, Cassidy J (2003) Constitutive nuclear factor-kappa B mRNA, protein overexpression and enhanced DNA-binding activity in thymidylate synthase inhibitor-resistant tumour cells. Br J Cancer 88(4) 624-629... 

Chen Y, Shu W, Chen W, Wu Q, Liu H, Cui G. 2007. Curcumin, both histone deacetylase and p300/CBP-specific inhibitor, represses the activity of nuclear factor kappa B and Notch 1 in Raji cells. Basic Clin Pharmacol Toxicol 101 427 433. 

Kim G. M., Xu J., Xu J. M., Song S. K., Yan P., Ku G., Xu X. M., and Hsu C. Y. (2001). Tumor necrosis factor receptor deletion reduces nuclear factor-kappa B activation, cellular inhibitor of apoptosis protein 2 expression, and functional recovery after traumatic spinal cord injury. J. Neurosci. 21 6617-6625. 

Although ingenol derivatives are highly potent inhibitors of HIV-1 replication in acutely infected cells, it was recently shown that some ingenol derivatives enhance HIV-1 replication in chronically infected cells, whether or not through activation of the nuclear factor kB (NF-kB) and protein kinase C (PKC). 

The flavonoid crysin and benzothiophenes have been shown to inhibit casein kinase II (CKII), a cellular protein that may regulate HIV-1 transcription by phosphorylating (other) cellular proteins involved in the HIV-1 transcription transactivation process. This mechanism of action is independent of the nuclear factor kB-driven transcription pathway. Thus, flavonoids interfere with HIV-1 transcription and hence prevent HIV expression in latently infected cells. Their specificity and usefulness as HIV transcription inhibitors remain to be assessed. 

Kubota T, Kushikata T, Fang J, Krueger JM. Nuclear factor-kappaB inhibitor peptide inhibits spontaneous and interleukin-1 beta-induced sleep. Am J Physiol Regul Integr Comp Physiol 2000 279 R404-R413. 

The interaction of NF-kB with IkB provides a wealth of examples of several different kinds of order-disorder processes. This work was started in our lab as a collaboration with Dr. E.A. Komives at the University of California, San Diego. Nuclear factor-kappaB (NF-kB) is a dimeric transcription factor widely employed for the transcription of stress-response genes, as it binds to kB upstream enhancer DNA sequences, where it recruits the transcriptional activator CBP. In an unstressed cell, the majority of the NF-kB resides in the cytoplasm, in complex with the inhibitor of NF-kB (IkB). Response to stress involves phosphorylation and ubiquitination of IkB and its subsequent degradation by the proteasome. The free NF-kB is transported to the nucleus, where it binds to the kB enhancer sequences and mediates the transcription of genes that include that of IkB, which acts subsequently to remove NF-kB from the DNA and return it to the cytoplasm as the NF-kB-IkB complex. 

Sunwoo JB, Chen Z, Dong G, Yeh N, Crowl Bancroft C, et al. 2001. Novel proteasome inhibitor PS-341 inhibits activation of nuclear factor-kappa B, cell survival, tumor growth, and angiogenesis in squamous cell carcinoma. Clin. Cancer Res. 7 1419-28... 

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