Role of 2-Arachidonoyl-Glycerol and CB1 Receptors in Orexin-A-Mediated Prevention of Oxygen-Glucose Deprivation-Induced Neuronal Injury.
endocannabinoids
ischemia
neuronal cell death
orexin-A
oxygen–glucose deprivation
radical oxygen species
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
20 06 2020
20 06 2020
Historique:
received:
01
06
2020
revised:
17
06
2020
accepted:
18
06
2020
entrez:
25
6
2020
pubmed:
25
6
2020
medline:
1
4
2021
Statut:
epublish
Résumé
Orexin-A (OX-A) protects the brain against oxidative stress-mediated ischemic injury. Since the endocannabinoid 2-arachidonoylglycerol (2-AG) and cannabinoid type-1 (CB1) receptors were previously shown to mediate some of the effects of OX-A exerted through the orexin-1 receptor (OX-1R), we investigated the involvement of 2-AG in OX-A-induced neuroprotection following oxygen and glucose deprivation (OGD) in mouse cortical neurons. OGD-induced reactive oxygen species (ROS) accumulation and neuronal death were prevented by both OX-A and arachidonyl-2'-chloroethylamide (ACEA), a synthetic CB1 receptor agonist, in a manner sensitive to OX-1R and CB1 receptor antagonists, SB334867 and AM251. OX-A stimulated 2-AG biosynthesis in cortical neurons. In neurons isolated from monoacylglycerol lipase (MAGL, a 2-AG hydrolyzing enzyme) null mice, 10-fold higher 2-AG concentrations were found and OGD failed to induce ROS production and cell death, whereas AM251 restored these noxious effects. OX-A-induced neuroprotection was mediated by the phosphoinositide-3-kinase/Akt (PI3K/Akt) survival pathway since both OX-A and ACEA induced phosphorylation of Akt and prevented OGD-induced cytochrome c release from the mitochondria, in a manner counteracted by SB334867 or AM251. Administration of OX-A reduced infarct volume and elevated brain 2-AG levels in a mouse model of transient ischemia. These results suggest that 2-AG and CB1 receptor mediate OX-A prevention of ischemia-induced neuronal apoptosis.
Identifiants
pubmed: 32575773
pii: cells9061507
doi: 10.3390/cells9061507
pmc: PMC7349736
pii:
doi:
Substances chimiques
Arachidonic Acids
0
Endocannabinoids
0
Glycerides
0
Orexins
0
Receptor, Cannabinoid, CB1
0
glyceryl 2-arachidonate
8D239QDW64
Glucose
IY9XDZ35W2
Oxygen
S88TT14065
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Références
Nat Rev Neurol. 2020 Jan;16(1):9-29
pubmed: 31831863
Biochem Biophys Res Commun. 2002 Jun 14;294(3):726-33
pubmed: 12056831
Rejuvenation Res. 2017 Apr;20(2):125-133
pubmed: 27814668
Cell. 1998 Sep 18;94(6):739-50
pubmed: 9753321
Cell. 1998 Feb 20;92(4):573-85
pubmed: 9491897
Nature. 2000 Oct 12;407(6805):802-9
pubmed: 11048732
Mol Pharmacol. 2010 Dec;78(6):996-1003
pubmed: 20855465
Proc Natl Acad Sci U S A. 2016 Apr 26;113(17):4759-64
pubmed: 27071101
Antioxid Redox Signal. 2011 Apr 15;14(8):1505-17
pubmed: 20812869
J Neurochem. 2007 Aug;102(4):1105-14
pubmed: 17484726
Endocrinology. 2007 Jan;148(1):148-59
pubmed: 17053024
Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18832-7
pubmed: 24191036
Cell. 1998 Aug 7;94(3):325-37
pubmed: 9708735
Endocr Rev. 2001 Apr;22(2):153-83
pubmed: 11294822
J Neurochem. 2007 Nov;103(3):904-13
pubmed: 17666049
Nat Struct Biol. 2001 May;8(5):394-401
pubmed: 11323712
J Gastroenterol. 2008;43(3):202-7
pubmed: 18373162
Am J Physiol Cell Physiol. 2002 Dec;283(6):C1567-91
pubmed: 12419707
Br J Pharmacol. 2013 Jun;169(4):784-93
pubmed: 23072382
J Neurosci. 2002 Dec 1;22(23):10291-301
pubmed: 12451129
Biomol Concepts. 2012 Oct;3(5):447-63
pubmed: 25436549
Chem Biol. 2007 Dec;14(12):1347-56
pubmed: 18096503
Cell. 1997 Nov 14;91(4):479-89
pubmed: 9390557
Acta Psychiatr Scand Suppl. 2007;(433):104-15
pubmed: 17280576
J Exp Med. 1996 Apr 1;183(4):1533-44
pubmed: 8666911
Neurobiol Dis. 2005 Oct;20(1):27-37
pubmed: 16137564
Neurosci Res. 2010 Oct;68(2):154-7
pubmed: 20600373
Nature. 1997 Aug 21;388(6644):773-8
pubmed: 9285589
Mol Pharmacol. 2012 Aug;82(2):156-67
pubmed: 22550093
J Endocrinol. 2008 Sep;198(3):511-21
pubmed: 18541646
J Cereb Blood Flow Metab. 1998 Nov;18(11):1239-47
pubmed: 9809513
Mol Cell Endocrinol. 2016 Jan 15;420:208-16
pubmed: 26549689
Front Neurosci. 2018 Nov 15;12:835
pubmed: 30524223
Brain Res. 1999 May 8;827(1-2):243-60
pubmed: 10320718
J Biol Chem. 2015 May 29;290(22):13669-77
pubmed: 25869131
J Cereb Blood Flow Metab. 1999 Jan;19(1):39-43
pubmed: 9886353
Biochem Pharmacol. 1995 Jun 29;50(1):83-90
pubmed: 7605349
Mol Cell Neurosci. 2005 Jan;28(1):189-94
pubmed: 15607953
J Neurochem. 2002 Oct;83(2):309-19
pubmed: 12423241
J Mol Neurosci. 2014 Jan;52(1):48-55
pubmed: 24243084
Methods Enzymol. 2008;441:73-82
pubmed: 18554530
Neuropsychopharmacology. 2016 Jan;41(2):508-20
pubmed: 26081302
Biochem Biophys Res Commun. 1995 Oct 4;215(1):89-97
pubmed: 7575630
J Neurosci. 1998 Dec 1;18(23):9996-10015
pubmed: 9822755
Nat Neurosci. 2010 Sep;13(9):1113-9
pubmed: 20729846
Cell Signal. 2019 Oct;62:109348
pubmed: 31233841
J Neurochem. 2000 Dec;75(6):2434-44
pubmed: 11080195
Neurosci Lett. 2012 Aug 22;524(1):30-4
pubmed: 22796468
Genes Dev. 1999 Nov 15;13(22):2905-27
pubmed: 10579998
Stroke. 2009 Jun;40(6):2157-64
pubmed: 19372445