NAMPT

Fig1. NAD biosynthetis from nicotinamide. (Antje Garten, 2011)

What is NAMPT protein?

NAMPT (nicotinamide phosphoribosyltransferase) gene is a protein coding gene which situated on the long arm of chromosome 7 at locus 7q22. This gene encodes a protein that catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, one step in the biosynthesis of nicotinamide adenine dinucleotide. The protein belongs to the nicotinic acid phosphoribosyltransferase (NAPRTase) family. The NAMPT protein is consisted of 491 amino acids and its molecular mass is approximately 55.5 kDa.

What is the function of NAMPT protein?

NAMPT catalyzes the production of nicotinamide adenine dinucleotide (NAD+), the precursor of NAD+, to maintain the level of NAD+ in cells, and NAD+ is involved in regulating a variety of biological processes, such as energy metabolism, DNA repair and cell aging. Secondly, NAMPT is also believed to be involved in the regulation of the immune system and inflammatory response, affecting the immune state of the body by affecting the function of immune cells.

NAMPT Related Signaling Pathway

The primary role of NAMPT protein is to catalyze the biosynthesis of nicotinamide adenine dinucleotide (NAD+), an important intracellular energy transfer molecule that interacts with a variety of enzymes and signaling pathways. Through its kinase activity, NAMPT protein can directly or indirectly regulate a variety of signaling pathways, including mTOR pathway, p53 pathway, NF-κB pathway, etc. In addition, NAMPT protein is also involved in cellular stress response, autophagy, anti-inflammatory and antioxidant processes.

NAMPT Related Diseases

NAMPT associated diseases include metabolic diseases such as obesity, diabetes, and metabolic syndrome, cardiovascular diseases such as coronary heart disease and hypertension, and neurological diseases such as Alzheimer's and Parkinson's disease. In addition, NAMPT protein is also closely related to the occurrence and development of tumors.

Fig2. PBEF is involved in the pathogenesis of several diseases. (Zhongjie Sun, 2013)

Bioapplications of NAMPT

The activity of NAMPT enzymes has been implicated in many diseases, including obesity, diabetes, cardiovascular disease, and neurodegenerative diseases, and therefore inhibitors and activators of NAMPT enzymes may be used to treat these diseases. Second, NAMPT is also involved in the regulation of the immune system and therefore can be used as a potential anti-inflammatory drug. In addition, due to its key role in energy metabolism, NAMPT has also been associated with liver protection, metabolic syndrome, and cancer treatment, among others.

Case study 1: Qianyang Liu, 2023

Nicotinamide phosphoribosyl transferase (NAMPT) is associated with various NAD+ -consuming enzymatic reactions. The precise role in intestinal mucosal immunity in necrotizing enterocolitis (NEC) is not well defined. Here, the researchers examined whether NAMPT inhibition by the highly specific inhibitor FK866 could alleviate intestinal inflammation during the pathogenesis of NEC.

NAMPT expression was upregulated in the human terminal ileum of human infants with NEC. FK866 inhibited intercellular NAD+ levels, macrophage M1 polarization, and the expression of NAD+ -dependent enzymes. Consistently, the capacity of macrophages to phagocytose zymosan particles, as well as antibacterial activity, were impaired by FK866, whereas NMN supplementation to restore NAD+ levels reversed the changes in phagocytosis and antibacterial activity.

Fig1. Western blot analysis was performed to examine NAMPT expression in ileal homogenates from human patients and controls.

Fig2. NAD+ concentrations were determined in the terminal ileum of animals that were treated as indicated (n = 6).

Case study 2: Justyna Gogola-Mruk, 2023

Ovarian cancer is characterized by recurrent peritoneal and distant metastasis. To survive in a non-adherent state, floating ovarian cancer spheroids develop mechanisms to resist anoikis. However, the mechanism by which visfatin induces anoikis resistance in ovarian cancer spheroids remains unknown. Here, the researchers aimed to assess wheather visfatin which possess anti-apoptotic properties can induce resistance of anoikis in ovarian cancer spheroids. Visfatin synthesis were examined using a commercial human visfatin ELISA Kit. Spheroid were exposed to visfatin and cell viability and caspase 3/7 activity were measured using CellTiter-Glo 3D cell viability assay and Caspase-Glo® 3/7 Assay System. mRNA and protein expression were analyzed by Real-time PCR and Western Blot analysis, respectively. higher expression and secretion of visfatin by epithelial than by granulosa ovarian cells, and in non-cancer tissues versus cancer tissues. Interestingly, visfatin increased the proliferation/apoptosis ratio in ovarian cancer spheroids. Specifically, both the intrinsic and extrinsic pathways of anoikis were regulated by visfatin.

Fig3. Effect of visfatin on the proliferation/apoptosis ratio in OVCAR-3, SKOV-3 and KGN cells.

Fig4. Dose-dependent effect of visfatin (10, 100 and 1000 ng/mL) on caspase-3 activity in KGN.

NAMPT has several biochemical functions, for example, cytokine activity,drug binding,nicotinamide phosphoribosyltransferase activity. Some of the functions are cooperated with other proteins, some of the functions could acted by NAMPT itself. We selected most functions NAMPT had, and list some proteins which have the same functions with NAMPT. You can find most of the proteins on our site.

NAMPT has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with NAMPT here. Most of them are supplied by our site. Hope this information will be useful for your research of NAMPT.

FTL;MT-ND1;IFITM3;DDA1;UBE2L6;GGT1;ADORA2A;AKT2;sseA;dcyD