Neural Regeneration Research ›› 2017, Vol. 12 ›› Issue (2): 283-289.doi: 10.4103/1673-5374.199006

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Edaravone protects against oxygen-glucose-serum deprivation/restoration-induced apoptosis in spinal cord astrocytes by inhibiting integrated stress response

Bin Dai1, 2, Ting Yan3, Yi-xing Shen1, You-jia Xu1, Hai-bin Shen2, Dong Chen2, Jin-rong Wang2, Shuang-hua He4, Qi-rong Dong1, Ai-liang Zhang4   

  1. 1 Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China; 
    2 Department of Orthopedics, Binhai County People’s Hospital, Binhai, Jiangsu Province, China; 
    3 Safety Assessment and Research Center for Drug, Pesticide and Veterinary Drug of Jiangsu Province, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, China; 
    4 Department of Orthopedics, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China
  • Received:2017-01-25 Online:2017-02-15 Published:2017-02-15
  • Contact: Qi-rong Dong or Ai-liang Zhang,dqrsdefy@163.com or ailiangzhang07@163.com.
  • Supported by:

    This work was supported by a grant from the Science & Technology Bureau of Changzhou City of China, No. CJ20130029.

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Abstract:

We previously found that oxygen-glucose-serum deprivation/restoration (OGSD/R) induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the integrated stress response, which involves protein kinase R-like endoplasmic reticulum kinase (PERK), eukaryotic initiation factor 2-alpha (eIF2α) and activating transcription factor 4 (ATF4). We hypothesized that edaravone, a low molecular weight, lipophilic free radical scavenger, would reduce OGSD/R-induced apoptosis of spinal cord astrocytes. To test this, we established primary cultures of rat astrocytes, and exposed them to 8 hours/6 hours of OGSD/R with or without edaravone (0.1, 1, 10, 100 μM) treatment. We found that 100 μM of edaravone significantly suppressed astrocyte apoptosis and inhibited the release of reactive oxygen species. It also inhibited the activation of caspase-12 and caspase-3, and reduced the expression of homologous CCAAT/enhancer binding protein, phosphorylated (p)-PERK, p-eIF2α, and ATF4. These results point to a new use of an established drug in the prevention of OGSD/R-mediated spinal cord astrocyte apoptosis via the integrated stress response.

Key words: nerve regeneration, edaravone, apoptosis, astrocytes, integrated stress response, reactive oxygen species, PERK, eIF2α, activating transcription factor 4, CCAAT/enhancer binding protein homologous protein, caspase-3, caspase-12, neural regeneration