Neural Regeneration Research ›› 2020, Vol. 15 ›› Issue (6): 1066-1070.doi: 10.4103/1673-5374.270314

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Proprotein convertase 1/3-mediated down-regulation of brain-derived neurotrophic factor in cortical neurons induced by oxygen-glucose deprivation

Xiang-Yang Zhang1, Feng Liu1, Yan Chen2, Wei-Chun Guo1, Zhao-Hui Zhang2   

  1. 1 Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
    2 Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
  • Online:2020-06-15 Published:2020-07-02
  • Contact: Yan Chen, PhD,chenyanzn@sina.com; Wei-Chun Guo, PhD,guoweichun@aliyun.com.
  • Supported by:
    This study was supported by the National Nature Science Foundation of China, No. 81501053 (to YC).

Abstract: Brain-derived neurotrophic factor (BDNF) has robust effects on synaptogenesis, neuronal differentiation and synaptic transmission and plasticity. The maturation of BDNF is a complex process. Proprotein convertase 1/3 (PC1/3) has a key role in the cleavage of protein precursors that are directed to regulated secretory pathways; however, it is not clear whether PC1/3 mediates the change in BDNF levels caused by ischemia. To clarify the role of PC1/3 in BDNF maturation in ischemic cortical neurons, primary cortical neurons from fetal rats were cultured in a humidified environment of 95% N2 and 5% CO2 in a glucose-free Dulbecco’s modified Eagle’s medium at 37°C for 3 hours. Enzyme-linked immunosorbent assays and western blotting showed that after oxygen-glucose deprivation, the secreted and intracellular levels of BDNF were significantly reduced and the intracellular level of PC1/3 was decreased. Transient transfection of cortical neurons with a PC1/3 overexpression plasmid followed by oxygen-glucose deprivation resulted in increased PC1/3 levels and increased BDNF levels. When levels of the BDNF precursor protein were reduced, the concentration of BDNF in the culture medium was increased. These results indicate that PC1/3 cleavage of BDNF is critical for the conversion of pro-BDNF in rat cortical neurons during ischemia. The study was approved by the Animal Ethics Committee of Wuhan University School of Basic Medical Sciences.

Key words: cortical neuron, ischemia, neurotrophin, oxygen-glucose deprivation, precursor protein of brain-derived neurotrophic factor,
proprotein convertase,
proprotein convertase 1/3