title: MG53 permeates through blood-brain barrier to protect ischemic brain injury.
abstract: Ischemic injury to neurons represents the underlying cause of stroke to the brain. Our previous studies identified MG53 as an essential component of the cell membrane repair machinery. Here we show that the recombinant human (rh)MG53 protein facilitates repair of ischemia-reperfusion (IR) injury to the brain. MG53 rapidly moves to acute injury sites on neuronal cells to form a membrane repair patch. IR-induced brain injury increases permeability of the blood-brain-barrier, providing access of MG53 from blood circulation to target the injured brain tissues. Exogenous rhMG53 protein can protect cultured neurons against hypoxia/reoxygenation-induced damages. Transgenic mice with increased levels of MG53 in the bloodstream are resistant to IR-induced brain injury. Intravenous administration of rhMG53, either prior to or after ischemia, can effectively alleviate brain injuries in rats. rhMG53-mediated neuroprotection involves suppression of apoptotic neuronal cell death, as well as activation of the pro-survival RISK signaling pathway. Our data indicate a physiological function for MG53 in the brain and suggest that targeting membrane repair or RISK signaling may be an effective means to treat ischemic brain injury.
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, P.R. China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.|Institute of Organ Transplantation, Huazhong University of Science and Technology - Tongji Medical College, Wuhan, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Haichang
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, P.R. China.
authors.forename: Ken
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, P.R. China.
authors.forename: Yukai
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, P.R. China.
authors.forename: Xinquan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, P.R. China.
authors.forename: Duofen
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Peihui
authors.initials: P
authors.lastname: Lin
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Ki Ho
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Zehua
authors.initials: Z
authors.lastname: Bian
authors.affiliation: Institute of Organ Transplantation, Huazhong University of Science and Technology - Tongji Medical College, Wuhan, P.R. China.
authors.forename: Zhishui
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Institute of Organ Transplantation, Huazhong University of Science and Technology - Tongji Medical College, Wuhan, P.R. China.
authors.forename: Nianqiao
authors.initials: N
authors.lastname: Gong
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Tan
authors.affiliation: Department of Physiology, Kansas City University of Medicine & Bioscience, Kansas City, MO, USA.
authors.forename: Jingsong
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Jianjie
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, P.R. China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002545:Brain Ischemia; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D000070584:Tripartite Motif Proteins
chemical_list: D002352:Carrier Proteins; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; C558399:TRIM72 protein, human; D000070584:Tripartite Motif Proteins
keywords: TRIM72; cell membrane repair; neuroprotection; stroke; tissue plasminogen activator