Open AccessMG53 permeates through blood-brain barrier to protect ischemic brain injury
Author(s) -
Yong-Gang Yao,
Bo Zhang,
Hua Zhu,
Haichang Li,
Yu Han,
Ken Chen,
Zhen Wang,
Jian Zeng,
Yukai Liu,
Xinquan Wang,
Yu Liu,
Duofen He,
PeiHui Lin,
Xinyu Zhou,
Ki Ho Park,
Zehua Bian,
Zhishui Chen,
Nianqiao Gong,
Tao Tan,
Jingsong Zhou,
Meng Zhang,
Jianjie Ma,
Chunyu Zeng
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.7965
Subject(s) - medicine , transplantation , stroke (engine) , neuroprotection , recombinant tissue plasminogen activator , ischemia , ischemic stroke , mechanical engineering , engineering , modified rankin scale
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.