1,720,988 research outputs found
Extracellular nicotinamide phosphoribosyltransferase, a new cancer metabokine
No full textIn this review, we focus on the secreted form of nicotinamide phosphoribosyltransferase (NAMPT); extracellular NAMPT (eNAMPT), also known as pre-B cell colony-enhancing factor or visfatin. Although intracellular NAMPT is a key enzyme in controlling NAD metabolism, eNAMPT has been reported to function as a cytokine, with many roles in physiology and pathology. Circulating eNAMPT has been associated with several metabolic and inflammatory disorders, including cancer. Because cytokines produced in the tumour micro-environment play an important role in cancer pathogenesis, in part by reprogramming cellular metabolism, future improvements in cancer immunotherapy will require a better understanding of the crosstalk between cytokine action and tumour biology. In this review, the knowledge of eNAMPT in cancer will be discussed, focusing on its immunometabolic function as a metabokine, its secretion, its mechanism of action and possible roles in the cancer micro-environment.</p
STUDY OF NAMPT ACTIVITY IN MELANOMA CELLS BY LC-ESI-MSn ANALYSES
No full textNicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in nicotinamide adenine dinucleotide NAD metabolism. It converts nicotinamide (NAM) to nicotinamide mononucleotide (NMN), via 5-phosphoribosyl pyrophosphate (PRPP) and Adenosine 5′-triphosphate (ATP). Afterwards, nicotinamide mononucleotide adenylyltransferase (NMNAT) synthesizes NAD from NMN in presence of ATP.
NAMPT is involved in many inflammatory and metabolic diseases, including cancer. Its activity is essential for maintaining the NAD pool especially in tumor cells, in which the activity of NAD degrading enzymes such as poly (ADP-ribose) polymerases (PARPs), mono (ADP-ribose) transferases (ARTs) and sirtuins is increased (Figure 1). Indeed, NAMPT is over-express by most of tumoural cells and its high levels are correlated to prognosis and overall survival. In this work, a new LC-ESI-MSn bioanalytical method was developed to evaluate all the analytes involved in the NAD homeostasis related to NAMPT activity and to deeply understand the mechanism of action of NAMPT in the B16 engineered melanoma cells. The method demonstrated to be sensitive, specific and very accurate for the quantification of six different molecules (AMP, ADP, ATP, NMN, NAD and NAM). The sample preparation was characterized by cells isolation followed by liquid-liquid extraction (LLE); all the analytes studied were separated by isocratic elution on a Luna HILIC column using acetonitrile and ammonium acetate buffer (pH 5,8, 100mM). The ESI MS detection was made either in positive or in negative scan, in MS2, SRM or MRM mode
Nicotinamide phosphoribosyltransferase (NAMPT) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH): interaction between moonlighting proteins as new molecular basis of cancer
No full textTriazole-curcuminoids: A new class of derivatives for 'tuning' curcumin bioactivities?
No full textCurcumin is a unique blend of pharmacophores responsible for the pleiotropy of this natural pigment. In the present study we have replaced the 1,3-dicarbonyl moiety with a 1,2,3-triazole ring to furnish a new class of triazole-curcuminoids as a possible strategy to generate new compounds with different potency and selectivity compared to curcumin. We obtained a proof-of-principle library of 28 compounds tested for their cytotoxicity (SY-SY5Y and HeLa cells) and for their ability to inhibit NF-κB. Furthermore, we also generated 1,3-dicarbonyl curcuminoids of selected click compounds. Triazole-curcuminoids lost their ability to be Michael's acceptors, yet maintained some of the features of the parent compounds and disclosed new ones. In particular, we found that some compounds were able to inhibit NF-κB without showing cytotoxicity, while others, unlike curcumin, activated NF-κB signalling. This validates the hypothesis that click libraries can be used to investigate the biological activities of curcumin as well as generate analogs with selected features
Differential deregulation of astrocytic calcium signalling by amyloid-β, TNFα, IL-1β and LPS
No full textIn Alzheimer's disease (AD), astrocytes undergo complex morphological and functional changes that include early atrophy, reactive activation and Ca2+ deregulation. Recently, we proposed a mechanism by which nanomolar Aβ42 deregulates mGluR5 and InsP3 receptors, the key elements of astrocytic Ca2+ signalling toolkit. To evaluate the specificity of these changes, we have now investigated whether the effects of Aβ42 on Ca2+ signalling machinery can be reproduced by pro-inflammatory agents (TNFα, IL-1β, LPS). Here we report that Aβ42 (100nM, 72h) significantly increased mRNA levels of mGluR5, InsP3R1 and InsP3R2, whereas pro-inflammatory agents reduced expression of these specific mRNAs. Furthermore, DHPG-induced Ca2+ signals and store operated Ca2+ entry (SOCE) were augmented in Aβ42-treated cells due to up-regulation of a set of Ca2+ signalling-related genes including TRPC1 and TRPC4. Opposite changes were observed when astrocytes were treated with TNFα, IL-1β and LPS. Last, the effects observed on SOCE by treating wild-type astrocytes with Aβ42 were also identified in untreated astrocytes from 3×Tg-AD animals, suggesting a link to the AD pathology. Our results demonstrate that effects of Aβ42 on astrocytic Ca2+ signalling differ from and may contrast to the effects of pro-inflammatory agents. © 2014 Elsevier Ltd
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