PMID- 24750959 OWN - NLM STAT- MEDLINE DCOM- 20141222 LR - 20211021 IS - 1755-5949 (Electronic) IS - 1755-5930 (Print) IS - 1755-5930 (Linking) VI - 20 IP - 6 DP - 2014 Jun TI - Extracellular visfatin has nicotinamide phosphoribosyltransferase enzymatic activity and is neuroprotective against ischemic injury. PG - 539-47 LID - 10.1111/cns.12273 [doi] AB - AIM: Visfatin, a novel adipokine, is predominantly produced by visceral adipose tissue and exists in intracellular and extracellular compartments. The intracellular form of visfatin is proved to be nicotinamide phosphoribosyltransferase (NAMPT) and exhibits neuroprotection through maintaining intracellular NAD(+) pool. However, whether extracellular form of visfatin has NAMPT activity and the effect of extracellular visfatin in cerebral ischemia are unknown. METHODS AND RESULTS: Plasma concentrations of visfatin, NAD(+) , and ATP were increased in mice upon cerebral ischemia. Cultured glia, but not neuron, was able to secrete visfatin. Oxygen-glucose deprivation (OGD) stress increased the secretion of visfatin from glia. Extracellular recombinant mouse wild-type visfatin, but not mouse H247A-mutant enzymatic-dead visfatin, had NAMPT enzymatic function in vitro. Treatment of wild-type visfatin, but not H247A-mutant enzymatic-dead visfatin, significantly attenuated detrimental effect of OGD on the cell viability and apoptosis in both cultured mouse neuron and glia. Treatment of neutralizing antibody, abolished the protective effect of extracellular visfatin on cell viability, but failed to block the antiapoptotic effect of extracellular visfatin. At last, we observed that plasma visfatin concentrations decreased in 6-month-old but not 3-month-old SHR-SP compared with that in age-matched Wistar-Kyoto rats. Inhibition of NAMPT enzymatic function of visfatin (by FK866) accelerated the occurrence of stroke in SHR-SP. CONCLUSIONS: Extracellular visfatin has NAMPT enzymatic activity and maybe be neuroprotective just as intracellular visfatin in cerebral ischemic injury. CI - (c) 2014 John Wiley & Sons Ltd. FAU - Zhao, Yan AU - Zhao Y AD - Department of Pharmacology, Second Military Medical University, Shanghai, China. FAU - Liu, Xin-Zhu AU - Liu XZ FAU - Tian, Wei-Wei AU - Tian WW FAU - Guan, Yun-Feng AU - Guan YF FAU - Wang, Pei AU - Wang P FAU - Miao, Chao-Yu AU - Miao CY LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140421 PL - England TA - CNS Neurosci Ther JT - CNS neuroscience & therapeutics JID - 101473265 RN - 0 (Acrylamides) RN - 0 (Antibodies) RN - 0 (Culture Media, Conditioned) RN - 0 (N-(4-(1-benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide) RN - 0 (Neuroprotective Agents) RN - 0 (Piperidines) RN - EC 2.4.2.12 (Nicotinamide Phosphoribosyltransferase) SB - IM MH - Acrylamides/pharmacology/therapeutic use MH - Animals MH - Animals, Newborn MH - Antibodies/pharmacology/therapeutic use MH - Brain Ischemia/drug therapy/*enzymology MH - Cell Hypoxia/drug effects MH - Cells, Cultured MH - Cerebral Cortex/cytology MH - Culture Media, Conditioned/pharmacology MH - Disease Models, Animal MH - Extracellular Fluid/drug effects/*metabolism MH - Gene Expression Regulation, Enzymologic/drug effects MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Neuroglia/drug effects/enzymology MH - Neurons/drug effects/enzymology MH - Neuroprotective Agents/blood/*metabolism/*therapeutic use MH - Nicotinamide Phosphoribosyltransferase/blood/genetics/immunology/*therapeutic use MH - Piperidines/pharmacology/therapeutic use MH - Rats MH - Rats, Inbred SHR MH - Rats, Inbred WKY MH - Stroke/drug therapy/genetics PMC - PMC6493111 OTO - NOTNLM OT - Cerebral ischemia OT - Extracellular OT - Neuroprotection OT - Nicotinamide phosphoribosyltransferase OT - Visfatin COIS- The authors declare no conflict of interest. EDAT- 2014/04/23 06:00 MHDA- 2014/12/23 06:00 PMCR- 2014/04/21 CRDT- 2014/04/23 06:00 PHST- 2014/01/21 00:00 [received] PHST- 2014/03/12 00:00 [revised] PHST- 2014/03/26 00:00 [accepted] PHST- 2014/04/23 06:00 [entrez] PHST- 2014/04/23 06:00 [pubmed] PHST- 2014/12/23 06:00 [medline] PHST- 2014/04/21 00:00 [pmc-release] AID - CNS12273 [pii] AID - 10.1111/cns.12273 [doi] PST - ppublish SO - CNS Neurosci Ther. 2014 Jun;20(6):539-47. doi: 10.1111/cns.12273. Epub 2014 Apr 21.