Edaravone protects against oxygen-glucose-serum deprivation/restoration-induced apoptosis in spinal cord astrocytes by inhibiting integrated stress response
机构:[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
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 (eIF2 alpha)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/ Rwith or without edaravone (0.1, 1, 10, 100 mu M) treatment. We found that 100 mu M 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-eIF2 alpha, 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.
基金:
This work was supported by a grant from the Science & Technology Bureau of Changzhou City of China, No. CJ20130029.
第一作者机构:[1]Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
通讯作者:
通讯机构:[1]Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China[4]Department of Orthopedics, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China
推荐引用方式(GB/T 7714):
Bin Dai,Ting Yan,Yi-xing Shen,et al.Edaravone protects against oxygen-glucose-serum deprivation/restoration-induced apoptosis in spinal cord astrocytes by inhibiting integrated stress response[J].NEURAL REGENERATION RESEARCH.2017,12(2):283-289.doi:10.4103/1673-5374.199006.
APA:
Bin Dai,Ting Yan,Yi-xing Shen,You-jia Xu,Hai-bin Shen...&Ai-liang Zhang.(2017).Edaravone protects against oxygen-glucose-serum deprivation/restoration-induced apoptosis in spinal cord astrocytes by inhibiting integrated stress response.NEURAL REGENERATION RESEARCH,12,(2)
MLA:
Bin Dai,et al."Edaravone protects against oxygen-glucose-serum deprivation/restoration-induced apoptosis in spinal cord astrocytes by inhibiting integrated stress response".NEURAL REGENERATION RESEARCH 12..2(2017):283-289