Oncotarget

Research Papers:

MG53 permeates through blood-brain barrier to protect ischemic brain injury

Yonggang Yao _, Bo Zhang, Hua Zhu, Haichang Li, Yu Han, Ken Chen, Zhen Wang, Jing Zeng, Yukai Liu, Xinquan Wang, Yu Li, Duofen He, Peihui Lin, Xinyu Zhou, Ki Ho Park, Zehua Bian, Zhishui Chen, Nianqiao Gong, Tao Tan, Jingsong Zhou, Meng Zhang, Jianjie Ma and Chunyu Zeng

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Oncotarget. 2016; 7:22474-22485. https://doi.org/10.18632/oncotarget.7965

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Abstract

Yonggang Yao1,*, Bo Zhang2,3,*, Hua Zhu2,*, Haichang Li2, Yu Han1, Ken Chen1, Zhen Wang1, Jing Zeng1, Yukai Liu1, Xinquan Wang1, Yu Li1, Duofen He1, Peihui Lin2, Xinyu Zhou2, Ki Ho Park2, Zehua Bian2, Zhishui Chen3, Nianqiao Gong3, Tao Tan2, Jingsong Zhou4, Meng Zhang5, Jianjie Ma2, Chunyu Zeng1

1Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, P.R. China

2Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA

3Institute of Organ Transplantation, Huazhong University of Science and Technology - Tongji Medical College, Wuhan, China

4Department of Physiology, Kansas City University of Medicine & Bioscience, Kansas City, MO, USA

5Department of Neurology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China

*These authors have contributed equally to this work

Correspondence to:

Jianjie Ma, e-mail: [email protected]

Chunyu Zeng, e-mail: [email protected]

Keywords: stroke, cell membrane repair, neuroprotection, TRIM72, tissue plasminogen activator

Received: December 30, 2015    Accepted: February 11, 2016    Published: March 08, 2016

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.


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