title: 2-Arachidonylglycerol Protects Primary Astrocytes Exposed to Oxygen-Glucose Deprivation Through a Blockade of NDRG2 Signaling and STAT3 Phosphorylation.
abstract: The human N-Myc downstream-regulated gene 2 (NDRG2) is expressed in astrocytes, and may be involved in the modulation of gliacyte function in the central nervous system. Our previous study found suppression of NDRG2 up-regulation in reactive astrocytes in cerebral ischemic tolerance. 2-Arachidonylglycerol (2-AG) can induce cerebral ischemic tolerance. However, the underlying mechanism of NDRG2 in cytoprotection induced by 2-AG in primary astrocytesis still unknown. In this study, we investigated the role of NDRG2 in cerebral ischemic tolerance induced by 2-AG after oxygen-glucose deprivation (OGD) in primary astrocytes. The results showed that primary astrocytes exposed to OGD resulted in marked increase of lactate dehydrogenase (LDH) release and decrease of methyl thiazolyl tetrazolium (MTT) reduction activity in comparison to control cultures. The levels of NDRG2 and phospho-signal transducer and activator of transcription 3 (pSTAT3) in the OGD group were comparably higher than those in the control group, and the up-regulation of NDRG2 and pSTAT3 was suppressed in NDRG2 siRNA group. The cell viability in the 2-AG group was higher than that in the OGD group, and transfecting the NDRG2 pSRL-CDH1-GFP vector reversed the protective effects of 2-AG. The levels of NDRG2 and pSTAT3 in the 2-AG group were lower than those in the OGD group. 2-AG suppressed STAT3 phosphorylation by decreased expression of NDRG2. In conclusion, 2-AG protects primary astrocytes exposed to oxygen-glucose deprivation through a blockade of NDRG2 signaling and STAT3 phosphorylation. These findings bring insight to the roles of NDRG2 in ischemic-hypoxic injury and provide novel potential targets for future potent clinical therapies on cerebral ischemia injury.
authors.affiliation: 1 Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University , Xi'an, Shaanxi Province, China .
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: 2 Department of Orthopaedics, Xijing Hospital, The Fourth Military Medical University , Xi'an, Shaanxi Province, China .
authors.forename: Mo
authors.initials: M
authors.lastname: Li
authors.affiliation: 1 Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University , Xi'an, Shaanxi Province, China .
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: 3 Department of Psychiatry, University of Ottawa Institute of Mental Health Research at the Royal , Ottawa, Canada .
authors.forename: Renee
authors.initials: R
authors.lastname: Kinden
authors.affiliation: 1 Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University , Xi'an, Shaanxi Province, China .
authors.forename: Heng
authors.initials: H
authors.lastname: Zhou
authors.affiliation: 1 Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University , Xi'an, Shaanxi Province, China .
authors.forename: Fan
authors.initials: F
authors.lastname: Guo
authors.affiliation: 1 Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University , Xi'an, Shaanxi Province, China .
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: 1 Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University , Xi'an, Shaanxi Province, China .
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001095:Arachidonic Acids / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D063388:Endocannabinoids / Q000494:pharmacology*; D005947:Glucose / Q000172:deficiency*; D005989:Glycerides / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D061251:Primary Cell Culture; D020011:Protective Agents / Q000494:pharmacology*; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; C507213:Ndrg2 protein, rat; D009419:Nerve Tissue Proteins; D020011:Protective Agents; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; C094503:glyceryl 2-arachidonate; D005947:Glucose