Inhibitor of nuclear factor

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]. 

Bayon Y, Alonso A, Crespo MS. 4-Trifluoromethyl derivatives of salicylate, triflusal and its main metabolite 2-hydroxy-4-trifluoromethylbenzoic acid, are potent inhibitor of nuclear factor kB activation. Br J Pharmacol 1999 126 1359-1466. 

Schreck R, Meier B, Mannel DN, Droge W, Baeuerle PA Dithiocarbamates as potent inhibitors of nuclear factor kB activation in intact cells. J Exp Med 1992 175 1181-1194. 

Members of the akuammiline alkaloid family also hold promise for treatment of pain and inflammation. Scholarisin I (60) and scholarisin VI (65) were claimed as selective inhibitors of COX-2, while pseudoakuammigine (13) has been reported to have in vivo anti-inflammatory and analgesic activity in rats observed via the carrageenan-induced paw edema and tail flick models respectively. " Picrinine (5) has also been su ested to have antiinflammatory and analgesic activity in mice based on results from various in vivo assays, while (Z)-alstoscholarine (29) was disclosed to be an inhibitor of nuclear factor-KB. ... 

Pradeep and Kuttan [24] established that piperine is a potent inhibitor of nuclear factor - kB (NF- kB), c-Fos, CREB, ATF-2, and proinflammatory cytokine gene expression in B16F-10 melanoma cells. 

Perivascular and intra-arterial administration of neutral sphingomyelinase or exogenous short-chain ceramide resulted in a potent concentration-dependent constriction of cortical venules, followed by increased venular waU permeability, post-capillary venule rupture and micro-hemorrhaging (Altura et al, 2002). Treatment with antioxidants, calcium channel blockers and inhibitors of nuclear factor-KB activation could attenuate the effects of neutral sphingomyelinase and ceramide. These results suggest that ceramide can play a role in vasoconstriction and may be involved in the mechanisms resulting in brain injury and stroke. 

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. 

Singh, S. et al.. Capsaicin is a potent inhibitor of nuclear transcription factor-KB activation by diverse agents, J. Immunol, 157, 4412, 1996. 

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... 

Inflammation is induced by the release of proinflammatory mediators from the cytosol of damaged or infected cells (Sect. 13.2.2). One of the first identified cytokines was an osteoclast activation factor later found to induce a multitude of other proinflammatory events, InterLeukin-1 (IL-1). A second was Tumor Necrosis Factor (TNF), more formally known as tumor necrosis factor-alpha, TNF-a (Sect. 13.2.2). The binding of these proteins to receptors on adjacent cells activates Nuclear Factor kappa B (NFkB), a protein in the leukocyte cytosol. The hgand-bound receptor indirectly phosphorylates an NFkB partner protein (Inhibitor of NFkB, IkB) in the cytosol. The phosphorylated IkB is targeted for destruction and its loss exposes a nuclear locahzation sequence on the NFkB protein which can now enter the nucleus where it induces the expression of important proteins, depending on the type of cell that is activated. ODAR is a Receptor Activator of Nuclear Factor kappa B (RANK), one of a large family of proinflammatory hgand receptors on leukocytes. 

NEMO kinase (regulatory subunit IKKy), NFkB (nuclear factor kappa B lymphoma) essential modulator, inhibitor of kappa kinase gamma (IKKy). Protein kinase C-interacting protein p62/sequestosome-l, is activated by interleukin IL-IP in sequence, it activates of nuclear factor NFkB in TNFa-stimulated cells (Zotti T et al Mol Immunol 2014 58 27-31). NEMO promotes vFFlP (Fas-associated death domain-like interleukin-1-converting enzyme inhibitory protein) expression by Kaposi sarcoma associated herpesvirus (KSHV) (Tolani B et al J Virol 2014 March 26 PMID 24672029). 

Yeast is of exceptional value in the study of cytochrome regulation. It is a facultative anaerobe, and the usual cytochromes disappear under anaerobic conditions. On aeration, cytochrome induction can be demonstrated in the living cell, and the role of oxygen and carbon source, as well as the effect of inhibitors, can be evaluated by a variety of means [19-25], Yeast affords opportunities for genetic analysis and lends itself to studies of the inheritance of nuclear factors governing cytochrome synthesis. Moreover, this organism readily develops a mitochondrial abnormality on treatment with acriflavine, the petite mutation, which permits examination of the role of cytoplasmic inheritance [26]. 

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