title: Globular adiponectin elicits neuroprotection by inhibiting NADPH oxidase-mediated oxidative damage in ischemic stroke.
abstract: Recent studies indicate that adiponectin can attenuate cerebral ischemic lesions via its functional area located in the C-terminal globular domain, which is called globular adiponectin (gAD). However, the mechanisms underlying this action remain unclear. In this study, we investigated the antioxidant properties of gAD during cerebral ischemia. Adult male C57BL/6 mice received an intracerebral injection of gAD with or without tetrabromocinnamic acid (TBCA, a NADPH oxidase activator). Mice were subjected to middle cerebral artery occlusion (MCAO) after gAD injection. Infarct volume, neurological function, the activity of antioxidant enzymes (superoxide dismutase [SOD], catalase), the content of malondialdehyde (MDA), and the expression of Bax, Bcl-2, cleaved caspase-3 and NADPH oxidase 2 (NOX2) were examined at 24h after MCAO. Infarct volume was attenuated in gAD-transduced mice when compared with mice in the MCAO group, with significant improvement in neurological function. In addition, neuronal apoptosis was attenuated, along with the expression of Bax/Bcl-2 and cleaved caspase 3. Furthermore, the activities of SOD and catalase increased, and the content of MDA reduced. However, TBCA blocked the effect of gAD on cerebral protection and its antioxidant abilities. Taken together, these results demonstrate that the neuroprotective action of gAD may result from the promotion of antioxidant capacity by inhibiting the NOX2 signaling system.
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, PR China; Department of Anesthesiology, Shaanxi Province People's Hospital, Xi'an 710068, Shaanxi Province, PR China.
authors.forename: W
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, PR China.
authors.forename: T
authors.initials: T
authors.lastname: Huo
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, PR China.
authors.forename: F
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, PR China.
authors.forename: Q
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, PR China. Electronic address: wangqiang@fmmu.edu.cn.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, PR China. Electronic address: mzkxlz@126.com.
authors.forename: L
authors.initials: L
authors.lastname: Xiong
mesh_terms: D052242:Adiponectin / Q000008:administration & dosage*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects*; D015427:Reperfusion Injury / Q000188:drug therapy; D020521:Stroke / Q000188:drug therapy* / Q000201:enzymology
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D000975:Antioxidants; D008562:Membrane Glycoproteins; D018696:Neuroprotective Agents; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
keywords: NADPH oxidase; cerebral ischemia; globular adiponectin; oxidative damage; stroke