Liproxstatin-1 Protects SH-SY5Y Cells by Inhibiting H2O2-Induced Excessive Mitophagy and Apoptosis

Oxidative stress is a critical factor in the pathogenesis of various neuronal disorders, causing cellular damage and mitochondrial dysfunction. This study aimed to explore the protective effects of liproxstatin-1 against H₂O₂-induced neural oxidative damage and elucidate the underlying mechanisms. Our findings demonstrated that 500 μmol/L H₂O₂ treatment induced mitochondrial dysfunction and Apoptosis in SH-SY5Y cells, while 1 μmol/L liproxstatin-1 effectively mitigated these cytotoxic effects by restoring mitochondrial integrity and enhancing cell viability. Furthermore, 500 μmol/L H₂O₂ exposure significantly suppressed the activation of the protein kinase B/ mammalian target of rapamycin signaling pathway and triggered excessive Mitophagy. Pretreatment with 1 μmol/L liproxstatin-1 attenuated the damage by H₂O₂, suggesting its protective role. Collectively, our results indicated that 500 μmol/L H₂O₂ induces cytotoxicity through oxidative damage, protein kinase B/ mammalian target of rapamycin pathway inhibition, and aberrant Mitophagy, ultimately leading to apoptosis; meanwhile, 1 μmol/L liproxstatin-1 counteracted these effects by preserving mitochondrial function, suppressing excessive Mitophagy, and inhibiting apoptotic pathways, thereby protecting SH-SY5Y cells from H₂O₂-induced cytotoxicity.

AKT/mTOR; H2O2; apoptosis; liproxstatin-1; mitophagy.