Neuroprotective effect of deferoxamine on erastin-induced ferroptosis in primary cortical neurons

• Published in: Neural regeneration research Vol. 15; no. 8; pp. 1539 - 1545
• Main Authors: Zhang, Yan, Fan, Bao-You, Pang, Yi-Lin, Shen, Wen-Yuan, Wang, Xu, Zhao, Chen-Xi, Li, Wen-Xiang, Liu, Chang, Kong, Xiao-Hong, Ning, Guang-Zhi, Feng, Shi-Qing, Yao, Xue
• Format: Journal Article
• Language: English
• Published: India Department of Orthopedics, General Hospital of Tianjin Medical University, Tianjin, China 01.08.2020; International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Tianjin, China%Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, Tianjin, China; Wolters Kluwer - Medknow
• Subjects: erastin; glutathione peroxidase 4; deferoxamine; ferroptosis; neuroprotection; reactive oxygen species; neurons; cystine/glutamate antiporter system light chain
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.274344

R453%R741%R363; The iron chelator deferoxamine has been shown to inhibit ferroptosis in spinal cord injury. However, it is unclear whether deferoxaminedirectly protects neurons from ferroptotic cell death. By comparing the survival rate and morphology of primary neurons and SH-SY5Ycells exposed to erastin, it was found that these cell types respond differentially to the duration and concentration of erastin treatment.Therefore, we studied the mechanisms of ferroptosis using primary cortical neurons from E16 mouse embryos. After treatment with 50 μMerastin for 48 hours, reactive oxygen species levels increased, and the expression of the cystine/glutamate antiporter system light chain andglutathione peroxidase 4 decreased. Pretreatment with deferoxamine for 12 hours inhibited these changes, reduced cell death, and amelio-rated cellular morphology. Pretreatment with the apoptosis inhibitor Z-DEVD-FMK or the necroptosis inhibitor necrostain-1 for 12 hoursdid not protect against erastin-induced ferroptosis. Only deferoxamine protected the primary cortical neurons from ferroptosis induced byerastin, confirming the specificity of the in vitro ferroptosis model. This study was approved by the Animal Ethics Committee at the Insti-tute of Radiation Medicine of the Chinese Academy of Medical Sciences, China (approval No. DWLL-20180913) on September 13, 2018.