title: Edaravone protects against oxygen-glucose-serum deprivation/restoration-induced apoptosis in spinal cord astrocytes by inhibiting integrated stress response.
abstract: We previously found that oxygen-glucose-serum deprivation/restoration (OGSD/R) induces apoptosis of spinal cord astrocytes, possiblyviacaspase-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 apoptosisviathe integrated stress response.
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China; Department of Orthopedics, Binhai County People's Hospital, Binhai, Jiangsu Province, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Dai
authors.affiliation: 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.
authors.forename: Ting
authors.initials: T
authors.lastname: Yan
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
authors.forename: Yi-Xing
authors.initials: YX
authors.lastname: Shen
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
authors.forename: You-Jia
authors.initials: YJ
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, Binhai County People's Hospital, Binhai, Jiangsu Province, China.
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Shen
authors.affiliation: Department of Orthopedics, Binhai County People's Hospital, Binhai, Jiangsu Province, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Binhai County People's Hospital, Binhai, Jiangsu Province, China.
authors.forename: Jin-Rong
authors.initials: JR
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China.
authors.forename: Shuang-Hua
authors.initials: SH
authors.lastname: He
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
authors.forename: Qi-Rong
authors.identifier: 0000-0003-2916-5792
authors.initials: QR
authors.lastname: Dong
authors.affiliation: Department of Orthopedics, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China.
authors.forename: Ai-Liang
authors.initials: AL
authors.lastname: Zhang
keywords: CCAAT/enhancer binding protein homologous protein; PERK; activating transcription factor 4; apoptosis; astrocytes; caspase-12; caspase-3; eIF2α; edaravone; integrated stress response; nerve regeneration; neural regeneration; reactive oxygen species