Mechanism of SOX10 in ferroptosis of hippocampal neurons after intracerebral hemorrhage via the miR-29a-3p/ACSL4 axis.

Intracerebral hemorrhage (ICH) is classified as a lethal neurological injury associated with cerebrovascular disorders. Ferroptosis is a unique form of cell death and participates in ICH pathogenesis. Herein, the role of SRY-box transcription factor 10 (SOX10) in ferroptosis of hippocampal neurons after ICH was investigated. The in vitro ICH models were established by treating immortalized mouse hippocampal cell line HT-22 with Hemin. Quantitative real-time polymerase chain reaction and Western blotting revealed that the transcription factor SOX10 and were decreased whereas acyl-CoA synthetase long-chain family member 4 (ACSL4) was increased in the ICH cell models. Subsequently, the assays of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, the commercial kits, and fluorescent labeling revealed that SOX10 overexpression improved cell viability, decreased the amount of reactive oxygen species (ROS) and Fe, and increased the amount of glutathione (GSH) and glutathione peroxidase 4 (GPX4) in ICH models. Thereafter, chromatin immunoprecipitation and dual-luciferase assays showed that SOX10 binding to the promoter region increased expression, and targeted and limited transcription. Rescue experiments showed that downregulation or ACSL4 overexpression expedited ferroptosis of Hemin-treated HT-22 cells. Taken together, SOX10 contributed to ferroptosis of hippocampal neurons after ICH via increasing to limit transcription. SOX10 promotes the expression of Mir-29a-3p by binding to the promoter region of Mir-29a-3p, thereby targeting the expression of ACSL4 and inhibiting the iron death of hippocampal neuronal cells in mice with ICH.