BNIP3 mediates pre-myelinating oligodendrocyte cell death in hypoxia and ischemia

Authors

  • Chengren Li,

    1. Department of Histology and Embryology, Faculty of Basic Medicine, Third Military Medical University, Chongqing, China
    2. Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
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    • These authors contributed equally to the work.
  • Teng Guan,

    1. Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
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    • These authors contributed equally to the work.
  • Xueping Chen,

    1. Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
    2. Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
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  • Wenyan Li,

    1. Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
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  • Qiyan Cai,

    1. Department of Histology and Embryology, Faculty of Basic Medicine, Third Military Medical University, Chongqing, China
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  • Jianqin Niu,

    1. Department of Histology and Embryology, Faculty of Basic Medicine, Third Military Medical University, Chongqing, China
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  • Lan Xiao,

    Corresponding author
    1. Department of Histology and Embryology, Faculty of Basic Medicine, Third Military Medical University, Chongqing, China
    • Address correspondence and reprint requests to J. Kong, Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, 745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada. E-mail: kongj@cc.umanitoba.ca or L. Xiao, Department of Histology and Embryology, Faculty of Basic Medicine, The Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China. E-mail: xiaolan35@hotmail.com

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  • Jiming Kong

    Corresponding author
    1. Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
    • Address correspondence and reprint requests to J. Kong, Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, 745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada. E-mail: kongj@cc.umanitoba.ca or L. Xiao, Department of Histology and Embryology, Faculty of Basic Medicine, The Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China. E-mail: xiaolan35@hotmail.com

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Abstract

Developing oligodendrocytes, collectively termed ‘pre-myelinating oligodendrocytes’ (preOLs), are vulnerable to hypoxic or ischemic insults. The underlying mechanism of this vulnerability remains unclear. Previously, we showed that Bcl-2⁄E1B-19K-interacting protein 3 (BNIP3), a proapoptotic member of the Bcl-2 family proteins, induced neuronal death in a caspase-independent manner in stroke. In this study, we investigated the role of BNIP3 in preOL cell death induced by hypoxia or ischemia. In primary oligodendrocyte progenitor cell (OPC) cultures exposed to oxygen–glucose deprivation, we found that BNIP3 was upregulated and levels of BNIP3 expression correlated with the death of OPCs. Up-regulation of BNIP3 was observed in preOLs in the white matter in a neonatal rat model of stroke. Knockout of BNIP3 significantly reduced death of preOLs in the middle cerebral artery occlusion model in mice. Our results demonstrate a role of BNIP3 in mediating preOLs cell death induced by hypoxia or ischemia, and suggest that BNIP3 may be a new target for protecting oligodendrocytes from death after stroke.

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Pre-myelinating oligodendrocytes (preOLs) are known to be highly vulnerable to ischemic insults. It remains unclear, however, how preOLs die. This study shows that BNIP3, a proapoptotic member of the Bcl-2 family proteins, is a mediator of hypoxia/ischemia-induced preOLs death. The BNIP3 cell death pathway may therefore be a new target for protecting oligodendrocytes from death after stroke.

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