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Induction of Neuronal Mitophagy in Acute Spinal Cord Injury in Rats

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Abstract

Autophagy and up-regulation of autophagy-associated proteins microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 have been shown to occur in spinal cord injury (SCI). Bcl-2/E1B-19 K-interacting protein 3 (BNIP3) and Nip-like protein X (NIX, also known as BNIP3L) are mitochondrial BH3-only proteins that are implicated in mitophagy. In this study, we show that mitophagy is activated in the injured neurons, and hypoxia-inducible proteins BNIP3, NIX, and p53 are upregulated after SCI. Numerous autophagosomes containing damaged mitochondria (mitophagosomes) were found in the injured neurons 24 h after SCI in rats by transmission electron microscopy; mitophagy, therefore, had occurred. Hypoxia-inducible proteins BNIP3, NIX, and p53 were upregulated in spinal cord neurons in both a rat model of SCI and cultured primary spinal neurons exposed to hypoxia. BNIP3 and NIX were transcriptionally regulated mainly by hypoxia-inducible factor-1α as well as p53 in cultured spinal cord neurons. This study provides direct morphological and biochemical evidence for mitophagy in the damaged neural tissue after SCI.

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Acknowledgments

This study was supported by Grants from the National Natural Science Foundation of China (81070980 to Z. Z.), CIHR and Canadian Stroke Network. We would like to thank Zhongfen Tao for technical assistance of electron microscope.

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Authors and Affiliations

  1. Department of Orthopedics, Xinqiao Hospital, The Third Military Medical University, Chongqing, 400037, China

    Datang Yu & Zhengfeng Zhang

  2. Department of Dermatology, Southwest Hospital, The Third Military Medical University, Chongqing, 400038, China

    Mingfang Li

  3. Institute of Immunology, The Third Military Medical University, Chongqing, 400038, China

    Bing Ni

  4. Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada

    Jiming Kong

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  1. Datang Yu
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  2. Mingfang Li
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  3. Bing Ni
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Correspondence to Jiming Kong or Zhengfeng Zhang.

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Yu, D., Li, M., Ni, B. et al. Induction of Neuronal Mitophagy in Acute Spinal Cord Injury in Rats. Neurotox Res 24, 512–522 (2013). https://doi.org/10.1007/s12640-013-9397-0

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  • DOI: https://doi.org/10.1007/s12640-013-9397-0

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