Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme for synthesis of nicotinamide adenine dinucleotide in mammalian cells. Recent studies show that Nampt also works as a cytokine that exerts insulin-mimetic effects by binding to the insulin receptor, induces B-cell differentiation, inhibits neutrophil apoptosis, and affects immune and inflammatory functions. This review is focused on current knowledge regarding the structure and function of Nampt and its roles in carcinogenesis.
Humans ; Neoplasms ; enzymology ; Nicotinamide Phosphoribosyltransferase ; metabolism ; physiology

Nicotinamide phosphoribosyltransferase (Nampt) is also called visfatin or pre-B-cell colony-enhancing factor. The functions of Nampt have been reported as a cytokine, an adipokine and the rate-limiting enzyme in nicotinamide adenine dinucleotide biosynthesis. As a pleiotropic multifunctional protein, Nampt is involved in a variety of physiological and pathological conditions including innate immunity, metabolic disorders, and stress; and Nampt also participates in inflammatory disorders such as acute lung injury, atherosclerosis, myocardial infarct, obesity, type 2 diabetes, and rheumatoid arthritis. The studies indicate that Nampt might be a potential target for pharmacological intervention against inflammatory diseases. We review research advances on the roles of Nampt in inflammation.
Animals ; Humans ; Inflammation ; enzymology ; Nicotinamide Phosphoribosyltransferase ; metabolism

Nicotinamide phosphoribosyl transferase (NAMPT) is the key enzyme for the synthesis of nicotinamide adenine dinucleotide (NAD), and also serves as a cytokine in mammalian cells. NAMPT is known to participate in biological responses such as glucose metabolism, inflammatory response and stress. Recent studies have revealed that NAMPT is closely associated with aging and age-related diseases such as diabetes, obesity, cancers, neuronal degeneration and cardiovascular diseases. Research on NAMPT may provide insight on prevention and treatment of related diseases.
Aging ; metabolism ; physiology ; Animals ; Humans ; Neoplasms ; metabolism ; physiopathology ; Nerve Degeneration ; metabolism ; physiopathology ; Nicotinamide Phosphoribosyltransferase ; metabolism ; physiology

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

Visfatin, also named nicotinamide phosphoribosyl transferase (NAMPT), is a cytokine secreted from adipose tissue. Visfatin can regulate immune action and is involved in the NAD+ salvage pathway. In addition, recent researches have shown that visfatin helps the regulation of glucose and lipid metabolism, especially in exercise-induced weight reduction for obesity. The aim of this review is to provide an overview of the contribution of visfatin gene polymorphisms to glucose and lipid metabolism and exercise-induced weight reduction in obesity.
Exercise ; physiology ; Glycolipids ; metabolism ; Humans ; Nicotinamide Phosphoribosyltransferase ; genetics ; physiology ; Obesity ; genetics ; metabolism ; Polymorphism, Genetic ; Weight Loss ; genetics

OBJECTIVETo observe the effect of recombinant human nicotinamide phosphoribosyl-transferase (NAMPT) on physiological/biochemical indexes and brain structure in mice.

METHODSWild type human recombinant NAMPT (10, 30 and 100 μg/kg) or H247A mutant NAMPT (with very weak enzymatic activity) were administrated by intravenous injection in mice once every 3 d for 32 d. The changes of body weight, blood pressure, heart rate, serum glucose, serum total cholesterol and triglyceride were determined, and the morphology of neuron, astrocyte and microglia in hippocampus were observed.

RESULTSThe injection of wild and mutated type NAMPT had no significant effect on body weight, blood pressure,heart rate, blood glucose, total cholesterol and triglyceride, and did not affect the morphology of neuron, astrocyte and microglia in hippocampus of mice.

CONCLUSIONElevation of plasma NAMPT may not induce metabolic and neuronal dysfunction in normal individual.

Animals ; Blood Glucose ; metabolism ; Brain ; anatomy & histology ; drug effects ; Cholesterol ; blood ; Cytokines ; pharmacology ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Nicotinamide Phosphoribosyltransferase ; pharmacology ; Recombinant Proteins ; pharmacology ; Triglycerides ; blood

Escherichia coli strain NZN111 is a promising candidate for the fermentative production of succinate. However, because lactate dehydrogenase and pyruvate formate lyase were inactivated in NZN111, this strain had an unbalanced NADH/NAD+ ratio and could not use glucose under anaerobic conditions. In this study, a recombinant strain E. coli NZN111/pTrc99a-pncB was constructed to overexpress the nicotinic acid phosphoribosyl transferase gene (pncB). Under anaerobic conditions with the addition of 0.5 mmol/L nicotinic acid and 0.3 mmol/L isopropyl beta-D-thiogalactopyranoside (IPTG), the specific nicotinic acid phosphoribosyl transferase (NAPRTase, EC 2.4.2.11) activity in the recombinant strain was 11-fold higher than that in E. coli NZN111, the concentration of NAD(H) was increased by 3.85-fold, especially the concentration of NAD+ was increased by 5.17-fold and NADH/NAD+ was decreased from 0.640 to 0.125. The recombinant strain regained the capability of growth and glucose utilization under anaerobic conditions.
Acetyltransferases ; genetics ; metabolism ; Anaerobiosis ; Escherichia coli ; classification ; genetics ; metabolism ; Fermentation ; Genetic Enhancement ; methods ; Glucose ; metabolism ; L-Lactate Dehydrogenase ; genetics ; metabolism ; NAD ; metabolism ; Nicotinamide Phosphoribosyltransferase ; biosynthesis ; genetics ; Succinic Acid ; metabolism

The aim of this study was to investigate the effect of suppression of nicotinamide phosphoribosyltransferase (NAMPT) expression on imatinib-sensitivity in chronic myelogenous leukemia (CML) cell line K562 and its mechanisms, NAMPT siRNA was synthesized and transfected into K562 cells. PI/Calcein staining technique was used to determine survival rate of transfected K562 cells at 48th hour after exposure to 1 µmol/L imatinib. MTS method was used to determine the proliferation changes of transfected K562 cell at 48th hour after exposure to different doses of imatinib, then half inhibitory concentration (IC(50)) was calculated. Expression of NAMPT at 3rd-48th hour after exposure to 1 µmol/L imatinib was determined by Western blot. To explore the effect of NAMPT-siRNA and imatinib on the expression of apoptosis-related genes, the microarray data from NCBI GEO Data-Sets was analyzed, then the results were confirmed by Western blot. The luciferase reporter assay was used to determine the effect of NAMPT and imatinib on transcriptional activity of NF-κB transcription factors. The results showed that after exposure to 1 µmol/L imatinib for 3 - 48 h, there was no significant change of NAMPT expression in K562 cells. The expression of NAMPT could be effectively inhibited by the NAMPT-siRNA. After exposure to 1 µmol/L of imatinib for 48 h, the survival rate of NAMPT-siRNA interference group was lower than that of negative control group (P < 0.05), indicating that suppression of NAMPT expression can increase the sensitivity of K562 cells to imatinib and enhance the killing effect of imatinib on K562 cells. The IC(50) of imatinib in NAMPT-siRNA interference group was the lowest compared with that of control group (P < 0.05) after exposure to different concentrations of imatinib for 48 h, the fitted survival curves showed that the slope of NAMPT-siRNA interference group was the largest ranging between 0.01 - 0.1 µmol/L of imatinib. Data mining of expression profiling indicated that the anti-apoptotic factor Bcl-2 decreased in K562 cells treated with either NAMPT-siRNA or imatinib, which was confirmed by Western blot. The inhibitory effect was much more significant when both NAMPT-siRNA and imatinib were used. The results of luciferase reporter assay showed that either NAMPT-siRNA or imatinib decreased transcriptional activity of NF-κB. The decreased effect was much more significant when both NAMPT-siRNA and imatinib were used. It is concluded that survival of K562 cells affected by imatinib may not be due to regulation of expression of NAMPT. When expression of NAMPT decreases, the K562 cells are more sensitive to imatinib, this may be related with the decreased transcriptional activity of NF-κB and its downstream effector Bcl-2.
Benzamides ; Cytokines ; antagonists & inhibitors ; metabolism ; Fusion Proteins, bcr-abl ; metabolism ; Humans ; Imatinib Mesylate ; K562 Cells ; NF-kappa B ; metabolism ; Nicotinamide Phosphoribosyltransferase ; antagonists & inhibitors ; metabolism ; Piperazines ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Pyrimidines ; pharmacology

OBJECTIVESTo study the expression of nicotinamide phosphoribosyl transferase (Nampt) and vascular endothelial growth factor-A (VEGF-A) in gastric carcinoma and investigate their correlations to clinicopathologic features and prognostic significance.

METHODSThe proteins of Nampt and VEGF-A in 68 specimens of gastric carcinoma and 59 specimens normal gastric tissue were detected by immunohistochemistry during January 2000 to December 2004, and the 68 patients were followed up.

RESULTSNampt protein was detected in the cytoplasm of both tissues, and Nampt in gastric carcinoma (13 ± 5) were significantly higher than that in normal gastric tissue (6 ± 3) (t = 7.46, P < 0.01). The expression of Nampt was correlated to invasive depth (F = 4.693, P = 0.034), lymph node metastasis (F = 4.027, P = 0.049), clinical TNM stage (F = 9.979, P = 0.002), but not to gender, age, tumor location, tumor size, differentiation (P > 0.05). The expression of Nampt is correlated with survival of patients that underwent surgical resection for gastric cancer. The survival rate of patients in negative of Nampt was very higher than that of the positive patients, and its co-expression with VEGF-A showed a trend towards poorer survival. The positive correlation was found between the expression of Nampt and VEGF-A in gastric carcinoma (r = 0.293, P = 0.015).

CONCLUSIONSThe expression of Nampt is positively correlated to that of VEGF-A in gastric carcinoma. The correlation between the expression of Nampt and VEGF-A in gastric carcinoma plays an important role cooperatively in carcinogenesis, development and metastasis of gastric carcinoma.

Adult ; Aged ; Aged, 80 and over ; Cytokines ; metabolism ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Nicotinamide Phosphoribosyltransferase ; metabolism ; Prognosis ; Stomach Neoplasms ; metabolism ; pathology ; Survival Rate ; Vascular Endothelial Growth Factor A ; metabolism

The aim of the current study is to investigate the effect of visfatin on cardiomyocyte hypertrophy. Cultured H9c2 cardiomyocytes were exposed to visfatin at different concentrations for different periods of time, and the markers of cardiomyocyte hypertrophy were detected. Moreover, pravastatin, the inhibitor of endoplasmic reticulum stress (ERS) or thapsigargin, an ERS agonist was used respectively to pre-treat the cells before visfatin stimulation. F-actin staining was performed to measure the cell surface change. The mRNA expressions of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and ERS markers including glucose-regulated protein 78(GRP78), C/EPB homologous protein (CHOP) and activating transcription factor 6 (ATF6) were assessed by real time RT-PCR. The change of protein level of GRP78 and CHOP was detected by Western blot. The experimental data demonstrated that exposure to 100 or 150 ng/mL concentrations of visfatin for 24 h, or 100 ng/mL of visfatin for 24 or 48 h, significantly increased the expression of markers for cardiomyocyte hypertrophy. Visfatin stimulation provoked ERS in H9c2 cells. Furthermore, pre-treatment with pravastatin partially inhibited the visfatin-induced mRNA expression of ANP and BNP in H9c2 cells, whereas thapsigargin promoted the visfatin-induced expression of cardiomyocyte hypertrophy markers. The results suggest that visfatin might induce cardiomyocyte hypertrophy via ERS -dependent pathways.
Actins ; Activating Transcription Factor 6 ; metabolism ; Animals ; Cell Line ; Heat-Shock Proteins ; metabolism ; Hypertrophy ; Myocytes, Cardiac ; cytology ; drug effects ; Natriuretic Peptide, Brain ; metabolism ; Nicotinamide Phosphoribosyltransferase ; pharmacology ; Rats ; Transcription Factor CHOP ; metabolism