PMID- 28499834 OWN - NLM STAT- MEDLINE DCOM- 20180525 LR - 20180525 IS - 1872-8111 (Electronic) IS - 0168-0102 (Linking) VI - 123 DP - 2017 Oct TI - N-stearoyltyrosine protects primary cortical neurons against oxygen-glucose deprivation-induced apoptosis through inhibiting anandamide inactivation system. PG - 8-18 LID - S0168-0102(17)30012-3 [pii] LID - 10.1016/j.neures.2017.04.019 [doi] AB - N-stearoylthrosine (NST), a synthesized anandamide (AEA) analogue, plays a neuroprotective role in neurodegenerative diseases and cerebrovascular diseases. Several studies have demonstrated that the endocannabinoids systems (ECS) are involved in the neuroprotective effects against cerebral ischemic injury. Oxygen-glucose deprivation (OGD)-induced neuronal injury elevated the levels of endocannabinoids and activated ECS. This research was conducted to investigate the neuroprotective effect of NST against OGD-induced neuronal injury in cultured primary cortical neurons and the potential mechanism involved. Cortical neurons were treated with NST at indicate concentrations for 30min prior to injury and OGD injured neurons were incubated with normal conditions for 0-24h. The best neuroprotective effect of NST against OGD-induced injury occurred at 10muM. All data indicated that the neuroprotective effect of NST against OGD-induced injury resulted from blocking anandamide membrane transporter (AMT) (IC(50)=11.74nM) and inhibiting fatty acid amide hydrolase activity (FAAH) (IC(50)=16.54nM). Our findings demonstrated that NST has an important role in cerebral ischemic injury pathological progression through activating cannabinoid receptors by inhibiting AEA inactivation system. These data suggested a potential role for NST in the therapeutic consideration of cerebral ischemic injury. However, inhibition of AEA inactivation system may provide a neuroprotective effect during cerebral ischemic injury. CI - Copyright (c) 2017. Published by Elsevier B.V. FAU - Cui, Heng-Jing AU - Cui HJ AD - Department of Pharmacy, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China. FAU - Liu, Sha AU - Liu S AD - Department of Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China. FAU - Yang, Rui AU - Yang R AD - Department of Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China. FAU - Fu, Guo-Hui AU - Fu GH AD - Department of Pathology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China. FAU - Lu, Yang AU - Lu Y AD - Department of Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China. Electronic address: huaxue@shsmu.edu.cn. LA - eng PT - Journal Article DEP - 20170510 PL - Ireland TA - Neurosci Res JT - Neuroscience research JID - 8500749 RN - 0 (Arachidonic Acids) RN - 0 (Endocannabinoids) RN - 0 (Enzyme Inhibitors) RN - 0 (Polyunsaturated Alkamides) RN - 0 (bcl-2-Associated X Protein) RN - 31C4KY9ESH (Nitric Oxide) RN - 42HK56048U (Tyrosine) RN - 57993-25-6 (N-stearoyltyrosine) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 3.5.- (Amidohydrolases) RN - EC 3.5.1.- (fatty-acid amide hydrolase) RN - IY9XDZ35W2 (Glucose) RN - S88TT14065 (Oxygen) RN - UR5G69TJKH (anandamide) SB - IM MH - Amidohydrolases/metabolism MH - Animals MH - Apoptosis/drug effects MH - Arachidonic Acids/*metabolism MH - Cell Hypoxia/*drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Cerebral Cortex/*cytology MH - Embryo, Mammalian MH - Endocannabinoids/*metabolism MH - Enzyme Inhibitors/pharmacology MH - Gene Expression Regulation/drug effects MH - Glucose/*deficiency/pharmacology MH - L-Lactate Dehydrogenase/metabolism MH - Neurons/*drug effects MH - Nitric Oxide/metabolism MH - Oxygen/pharmacology MH - Polyunsaturated Alkamides/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Tyrosine/*analogs & derivatives/pharmacology MH - bcl-2-Associated X Protein/metabolism OTO - NOTNLM OT - Anandamide (AEA) OT - Anandamide inactivation system OT - Endocannabinoid system (ECS) OT - N-stearoylthrosine (NST) OT - Oxygen-glucose deprivation (OGD) EDAT- 2017/05/14 06:00 MHDA- 2018/05/26 06:00 CRDT- 2017/05/14 06:00 PHST- 2017/01/06 00:00 [received] PHST- 2017/04/13 00:00 [revised] PHST- 2017/04/17 00:00 [accepted] PHST- 2017/05/14 06:00 [pubmed] PHST- 2018/05/26 06:00 [medline] PHST- 2017/05/14 06:00 [entrez] AID - S0168-0102(17)30012-3 [pii] AID - 10.1016/j.neures.2017.04.019 [doi] PST - ppublish SO - Neurosci Res. 2017 Oct;123:8-18. doi: 10.1016/j.neures.2017.04.019. Epub 2017 May 10.