title: Vinexin-β deficiency protects against cerebral ischaemia/reperfusion injury by inhibiting neuronal apoptosis.
abstract: Vinexin-β is an adaptor protein that regulates cell adhesion, cytoskeletal organization and signal transduction. Our previous work showed that Vinexin-β protects against cardiac hypertrophy. However, its function in stroke is largely unknown. In the present study, we observed a significant increase in Vinexin-β expression in both human intracerebral haemorrhage and mouse cerebral ischaemia/reperfusion (I/R) injury model, indicating that Vinexin-β is involved in stroke. Next, using Vinexin-β knockout mice, we further demonstrated that Vinexin-β deficiency significantly protected against cerebral I/R injury, as demonstrated by a dramatic decrease in the infarct volume and an improvement in neurological function. Additionally, immunofluorescence and western blotting showed that the deletion of Vinexin-β attenuated neuronal apoptosis. Mechanically, we found that Akt signalling was up-regulated in the brains of the Vinexin-β knockout mice compared with those of the WT control mice after ischaemic injury. Taken together, our results demonstrate that the deletion of Vinexin-β potently protects against ischaemic injury by inhibiting neuronal apoptosis, and this effect may occur via the up-regulation of Akt signalling. Our findings revealed that Vinexin-β acts as a novel modulator of ischaemic injury, suggesting that Vinexin-β may represent an attractive therapeutic target for the prevention of stroke.
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Mingchang
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute, Wuhan University, Wuhan, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute, Wuhan University, Wuhan, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute, Wuhan University, Wuhan, China.|College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute, Wuhan University, Wuhan, China.
authors.forename: Ankang
authors.initials: A
authors.lastname: Zheng
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute, Wuhan University, Wuhan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute, Wuhan University, Wuhan, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000378:metabolism*; D009474:Neurons / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D009124:Muscle Proteins; C486523:SORBS3 protein, human; C117452:Sorbs3 protein, mouse; C512725:Sorbs3 protein, rat
keywords: Akt; Vinexin-β; apoptosis; knockout mice; stroke; transient middle cerebral artery occlusion