Neurological research · 2026
SP1 and ELAVL1 cooperatively regulate ALOX15-mediated ferroptosis in an OGD/R-Induced SK-N-SH cell model of cerebral infarction.
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Liang Shunli, Wu You, Zhang Rongbo, Xu Linsheng, Xie Fangping
Аннотация
BACKGROUND: Cerebral infarction (CI) is associated with high incidence and mortality rates. This study aimed to investigate the role and molecular mechanism of arachidonate 15-lipoxygenase (ALOX15) in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced SK-N-SH cells.
METHODS: An in vitro OGD/R model was established using SK-N-SH cells. The gene expression levels were assessed by RT-qPCR and western blotting. Cell proliferation and apoptosis were evaluated using the 5-Ethynyl-2'-deoxyuridine (EdU) assay and flow cytometry. Ferroptosis-related markers, including reactive oxygen species (ROS), Fe2+, and malondialdehyde (MDA), were measured. Bioinformatics analysis, dual-luciferase reporter, and chromatin immunoprecipitation (ChIP) assays were used to validate the transcriptional regulation of ALOX15 by SP1. The interaction between ELAV-like RNA-binding protein 1 (ELAVL1) and ALOX15 was analyzed using RNA-binding protein database analysis. In vivo, a middle cerebral artery occlusion (MCAO) model was used to assess the effects of ALOX15 silencing on cerebral infarct volume and neurological deficits.
RESULTS: ALOX15 was upregulated in CI patient tissues and OGD/R-treated SK-N-SH cells. Silencing ALOX15 alleviated OGD/R-induced SK-N-SH cell injury and ferroptosis. Specificity protein 1 (SP1) transcriptionally activated ALOX15 expression, promoting cell damage and ferroptosis. Additionally, ELAVL1 stabilized ALOX15 mRNA, further enhancing its expression and contributing to OGD/R-induced injury and ferroptosis. In the MCAO model, ALOX15 knockdown reduced infarct volume and improved neurological outcomes.
CONCLUSION: SP1 and ELAVL1 regulated ALOX15 to drive OGD/R-induced SK-N-SH cell injury and ferroptosis. These findings highlight the SP1/ELAVL1-ALOX15 axis as a potential therapeutic target for mitigating brain injury in CI, providing a translational basis for future interventions.
METHODS: An in vitro OGD/R model was established using SK-N-SH cells. The gene expression levels were assessed by RT-qPCR and western blotting. Cell proliferation and apoptosis were evaluated using the 5-Ethynyl-2'-deoxyuridine (EdU) assay and flow cytometry. Ferroptosis-related markers, including reactive oxygen species (ROS), Fe2+, and malondialdehyde (MDA), were measured. Bioinformatics analysis, dual-luciferase reporter, and chromatin immunoprecipitation (ChIP) assays were used to validate the transcriptional regulation of ALOX15 by SP1. The interaction between ELAV-like RNA-binding protein 1 (ELAVL1) and ALOX15 was analyzed using RNA-binding protein database analysis. In vivo, a middle cerebral artery occlusion (MCAO) model was used to assess the effects of ALOX15 silencing on cerebral infarct volume and neurological deficits.
RESULTS: ALOX15 was upregulated in CI patient tissues and OGD/R-treated SK-N-SH cells. Silencing ALOX15 alleviated OGD/R-induced SK-N-SH cell injury and ferroptosis. Specificity protein 1 (SP1) transcriptionally activated ALOX15 expression, promoting cell damage and ferroptosis. Additionally, ELAVL1 stabilized ALOX15 mRNA, further enhancing its expression and contributing to OGD/R-induced injury and ferroptosis. In the MCAO model, ALOX15 knockdown reduced infarct volume and improved neurological outcomes.
CONCLUSION: SP1 and ELAVL1 regulated ALOX15 to drive OGD/R-induced SK-N-SH cell injury and ferroptosis. These findings highlight the SP1/ELAVL1-ALOX15 axis as a potential therapeutic target for mitigating brain injury in CI, providing a translational basis for future interventions.