title: NAMPT protects against 6-hydroxydopamine-induced neurotoxicity in PC12 cells through modulating SIRT1 activity.
abstract: Parkinson's disease (PD) is the second most common progressive neurodegenerative movement disorder. Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the first rate‑limiting step in the nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway in mammals, is a substrate for NAD+‑dependent enzymes, such as sirtuin 1 (SIRT1), and contributes to cell fate decisions. However, the role of NAMPT in PD has remained to be fully elucidated. In the present study, PC12 cells were treated with the neurotoxin 6-hydroxydopamine (6‑OHDA) to establish an in vitro model of PD, following which an obvious inhibitory effect on the levels of NAMPT and NAD+ as well as the NAD+/NADH ratio was detected. In addition, pre‑incubation with FK866, a highly specific NAMPT inhibitor, enhanced the inhibitory effects of 6‑OHDA on the viability of PC12, while pre‑incubation with nicotinamide mononucleotide (NMN), am enzymatic product of NAMPT, had the opposite effect. Furthermore, it was revealed that NMN markedly attenuated 6‑OHDA‑induced decreases in superoxide dismutase activity and glutathione levels, as well as 6‑OHDA‑induced increases in malondialdehyde and lactate dehydrogenase in PC12 cells. Furthermore, 6‑OHDA significantly reduced SIRT1 activity in PC12 cells, which was inhibited by NMN. The pharmacological activator resveratrol also significantly inhibited 6‑OHDA‑mediated decreases in PC12 cell viability while reversing 6‑OHDA‑induced decreases in SIRT1 levels. The results of the present study suggested that NMT protected against 6‑OHDA‑induced decreases in PC12 cell viability, and that SIRT1 activation had a role in this process. Treatment with NMN to activate SIRT1 may represent a novel therapeutic strategy for treating PD.
authors.affiliation: Department of Neurology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zou
authors.affiliation: Department of Massage, The Third Affiliated Hospital of Zhejiang Province Traditional Chinese Medical University, Hangzhou, Zhejiang 310012, P.R. China.
authors.forename: Shao-Qing
authors.initials: SQ
authors.lastname: Guo
authors.affiliation: Department of Neurology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Hu
authors.affiliation: Department of Neurology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China.
authors.forename: Wei-Lang
authors.initials: WL
authors.lastname: Li
mesh_terms: D000178:Acrylamides / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D009537:Nicotinamide Mononucleotide / Q000378:metabolism / Q000494:pharmacology; D054409:Nicotinamide Phosphoribosyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity*; D016716:PC12 Cells; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000178:Acrylamides; D016207:Cytokines; C480543:N-(4-(1-benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide; D010880:Piperidines; D009537:Nicotinamide Mononucleotide; D008315:Malondialdehyde; D016627:Oxidopamine; D007770:L-Lactate Dehydrogenase; D054409:Nicotinamide Phosphoribosyltransferase; C504970:nicotinamide phosphoribosyltransferase, rat; C488368:Sirt1 protein, rat; D056564:Sirtuin 1