Nicotinamide phosphoribosyltransferase secreted from microglia <i>via</i> exosome during ischemic injury

Lu, Yun-Bi; Chen, Chen-Xiang; Huang, Jing; Tian, Yuxin; Xie, Xiaogao; Yang, Ping; Wu, Ming; Tang, Chun; Zhang, Weiping

doi:10.1111/jnc.14811

Cited by 30 publications

(25 citation statements)

References 52 publications

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“…EV-contained-eNAMPT is internalized into cells, enhancing NAD synthesis (120). The same conclusion was obtained by another group identifying that eNAMPT is actively secreted via exosomes from microglia during neuroinflammation due to ischemic injury (121). However, this mechanism of secretion could be context dependent: in fact in 3T3-L1 adipocytes eNAMPT release and secretion do not appear to occur through microvesicles (113).…”

Section: Namptsupporting

confidence: 55%

NAMPT and NAPRT: Two Metabolic Enzymes With Key Roles in Inflammation

2020

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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.

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Section: Namptsupporting

confidence: 55%

NAMPT and NAPRT: Two Metabolic Enzymes With Key Roles in Inflammation

2020

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“…These EVs were enriched with TNF and IL-6, and the inhibition of the TNF pathway significantly reduced this process [121]. Another study showed that microglia secreted nicotinamide phosphoribosyltransferase (NAMPT), which is a protein that stimulates pro-inflammatory signaling cascades via EVs upon the induction of pathological conditions like ischemia [122].…”

Section: Glial Cell-derived Evs Under Stroke Conditionmentioning

confidence: 99%

From Tumor Metastasis towards Cerebral Ischemia—Extracellular Vesicles as a General Concept of Intercellular Communication Processes

Zheng

Bähr

Doeppner

2019

IJMS

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Extracellular vesicles (EVs) have been tremendous carriers in both experimental and translational science. These vesicles—formerly regarded as artifacts of in vitro research—have a heterogeneous population of vesicles derived from virtually all eukaryotic cells. EVs consist of a bilayer lipid structure with a diameter of about 30 to 1000 nm and have a characteristic protein and non-coding RNA content that make up different forms of EVs such as exosomes, microvesicles, and others. Despite recent progress in the EV field, which is known to serve as potential biomarkers and therapeutic tools under various pathological conditions, fundamental questions are yet to be answered. This short review focuses on recently reported data regarding EVs under pathological conditions with a particular emphasis on the role of EVs under such different conditions like tumor formation and cerebral ischemia. The review strives to point out general concepts of EV intercellular communication processes that might be vital to both diagnostic and therapeutic strategies in the long run.

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“…However, while Nam is present in the extracellular space, PRPP is undetectable [33]. The recent evidence that eNAMPT is carried in extracellular vesicles suggests that it might enhance NMN and hence NAD biosynthesis upon internalization in the target tissue [162,163]. This finding also discloses a possible mechanism of NAMPT secretion through exosomes and microvesicles, which is in keeping with the lack of cytokinespecific secretion sequences in the protein, and the inability of typical inhibitors of Golgi-dependent protein secretion to inhibit NAMPT secretion.…”

Section: Nicotinamide Phosphoribosyltransferasementioning

confidence: 99%

Enzymology of extracellular NAD metabolism

Gasparrini

Sorci

Raffaelli

2021

Cell. Mol. Life Sci.

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Extracellular NAD represents a key signaling molecule in different physiological and pathological conditions. It exerts such function both directly, through the activation of specific purinergic receptors, or indirectly, serving as substrate of ectoenzymes, such as CD73, nucleotide pyrophosphatase/phosphodiesterase 1, CD38 and its paralog CD157, and ecto ADP ribosyltransferases. By hydrolyzing NAD, these enzymes dictate extracellular NAD availability, thus regulating its direct signaling role. In addition, they can generate from NAD smaller signaling molecules, like the immunomodulator adenosine, or they can use NAD to ADP-ribosylate various extracellular proteins and membrane receptors, with significant impact on the control of immunity, inflammatory response, tumorigenesis, and other diseases. Besides, they release from NAD several pyridine metabolites that can be taken up by the cell for the intracellular regeneration of NAD itself. The extracellular environment also hosts nicotinamide phosphoribosyltransferase and nicotinic acid phosphoribosyltransferase, which inside the cell catalyze key reactions in NAD salvaging pathways. The extracellular forms of these enzymes behave as cytokines, with pro-inflammatory functions. This review summarizes the current knowledge on the extracellular NAD metabolome and describes the major biochemical properties of the enzymes involved in extracellular NAD metabolism, focusing on the contribution of their catalytic activities to the biological function. By uncovering the controversies and gaps in their characterization, further research directions are suggested, also to better exploit the great potential of these enzymes as therapeutic targets in various human diseases.

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Nicotinamide phosphoribosyltransferase secreted from microglia via exosome during ischemic injury

Cited by 30 publications

References 52 publications

NAMPT and NAPRT: Two Metabolic Enzymes With Key Roles in Inflammation

NAMPT and NAPRT: Two Metabolic Enzymes With Key Roles in Inflammation

From Tumor Metastasis towards Cerebral Ischemia—Extracellular Vesicles as a General Concept of Intercellular Communication Processes

Enzymology of extracellular NAD metabolism

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