title: Mn-SOD Upregulation by Electroacupuncture Attenuates Ischemic Oxidative Damage via CB1R-Mediated STAT3 Phosphorylation.
abstract: Electroacupuncture (EA) pretreatment elicits the neuroprotective effect against cerebral ischemic injury through cannabinoid receptor type 1 receptor (CB1R). In current study, we aimed to investigate whether the signal transducer and activator of transcription 3 (STAT3) and manganese superoxide dismutase (Mn-SOD) were involved in the antioxidant effect of EA pretreatment through CB1R. At 2 h after EA pretreatment, focal cerebral ischemic injury was induced by transient middle cerebral artery occlusion for 60 min in C57BL/6 mice. The expression of Mn-SOD in the penumbra was assessed by Western blot and immunoflourescent staining at 2 h after reperfusion. In the presence or absence of Mn-SOD small interfering RNA (siRNA), the neurological deficit score, the infarct volume, the terminal deoxynucleotidyl transferase-mediated dUDP-biotin nick end labeling (TUNEL) staining, and oxidative stress were evaluated. Furthermore, the Mn-SOD protein expression and phosphorylation of STAT3 at Y705 were also determined in the presence and absence of CB1R antagonists (AM251, SR141716) and CB1R agonists (arachidonyl-2-chloroethylamide (ACEA), WIN 55,212-2). EA pretreatment upregulated the Mn-SOD protein expression and Mn-SOD-positive neuronal cells at 2 h after reperfusion. EA pretreatment also attenuated oxidative stress, inhibited cellular apoptosis, and induced neuroprotection against ischemic damage, whereas these beneficial effects of EA pretreatment were reversed by knockdown of Mn-SOD. Mn-SOD upregulation and STAT3 phosphorylation by EA pretreatment were abolished by two CB1R antagonists, while pretreatment with two CB1R agonists increased the expression of Mn-SOD and phosphorylation level of STAT3. Mn-SOD upregulation by EA attenuates ischemic oxidative damage through CB1R-mediated STAT3 phosphorylation in stroke mice, which may represent one new mechanism of EA pretreatment-induced neuroprotection against cerebral ischemia.
authors.affiliation: Department of Anesthesiology Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
authors.forename: Sisi
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Physiology, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Xiyao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Anesthesiology Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhai
authors.affiliation: Department of Anesthesiology Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China. caimin@fmmu.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Cai
authors.affiliation: Department of Anesthesiology Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China. wangqiang@fmmu.edu.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D015671:Electroacupuncture; D055785:Gene Knockdown Techniques; D008297:Male; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D000066829:Neuroprotection; D018384:Oxidative Stress; D010766:Phosphorylation; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D043884:Receptor, Cannabinoid, CB1; D050796:STAT3 Transcription Factor; D013482:Superoxide Dismutase
keywords: Cannabinoid receptor type 1 receptor (CB1R); Cerebral ischemia; Electroacupuncture; Manganese superoxide dismutase (Mn-SOD); Oxidative damage; Signal transducer and activator of transcription 3 (STAT3)