Audrito Valentina, Messana Vincenzo Gianluca, Deaglio Silvia
Laboratory of Tumor Immunogenetics, Department of Medical Sciences, University of Turin, Turin, Italy.
Front Oncol. 2020 Mar 19;10:358. doi: 10.3389/fonc.2020.00358. eCollection 2020.
Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPRT) are two intracellular enzymes that catalyze the first step in the biosynthesis of NAD from nicotinamide and nicotinic acid, respectively. By fine tuning intracellular NAD levels, they are involved in the regulation/reprogramming of cellular metabolism and in the control of the activity of NAD-dependent enzymes, including sirtuins, PARPs, and NADases. However, during evolution they both acquired novel functions as extracellular endogenous mediators of inflammation. It is well-known that cellular stress and/or damage induce release in the extracellular milieu of endogenous molecules, called alarmins or damage-associated molecular patterns (DAMPs), which modulate immune functions through binding pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), and activate inflammatory responses. Increasing evidence suggests that extracellular (e)NAMPT and eNAPRT are novel soluble factors with cytokine/adipokine/DAMP-like actions. Elevated eNAMPT were reported in several metabolic and inflammatory disorders, including obesity, diabetes, and cancer, while eNAPRT is emerging as a biomarker of sepsis and septic shock. This review will discuss available data concerning the dual role of this unique family of enzymes.
烟酰胺磷酸核糖转移酶（NAMPT）和烟酸磷酸核糖转移酶（NAPRT）是两种细胞内酶，分别催化从烟酰胺和烟酸生物合成NAD的第一步。通过微调细胞内NAD水平，它们参与细胞代谢的调节/重编程以及对NAD依赖性酶（包括沉默调节蛋白、聚（ADP-核糖）聚合酶和NAD酶）活性的控制。然而，在进化过程中，它们都获得了作为炎症细胞外内源性介质的新功能。众所周知，细胞应激和/或损伤会诱导内源性分子释放到细胞外环境中，这些分子被称为警报素或损伤相关分子模式（DAMPs），它们通过与模式识别受体（PRRs）如Toll样受体（TLRs）结合来调节免疫功能，并激活炎症反应。越来越多的证据表明，细胞外（e）NAMPT和eNAPRT是具有细胞因子/脂肪因子/DAMP样作用的新型可溶性因子。在包括肥胖、糖尿病和癌症在内的几种代谢和炎症性疾病中，均报道了eNAMPT升高，而eNAPRT正在成为脓毒症和脓毒性休克的生物标志物。本综述将讨论有关这一独特酶家族双重作用的现有数据。
