Manganese Dioxide Nanoparticles Protect PC12 Cells Against H2O2-Induced Oxidative Stress Injury by Regulating PI3K/Akt-Mediated Autophagy.

Abstract

Background: Oxidative stress-mediated neuronal injury is critically involved in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. Manganese dioxide (MnO₂), owing to its intrinsic reactive oxygen species (ROS)-scavenging capacity, has emerged as a promising neuroprotective candidate; however, the underlying molecular mechanisms remain insufficiently defined. Methods: Bovine serum albumin-templated MnO₂ nanoparticles (BSA-MnO₂ NPs) were synthesized, and their protective effects were evaluated in H₂O₂-treated PC12 cells. Results: BSA-MnO₂ NPs significantly inhibited H₂O₂-induced reductions in cell viability, ROS overproduction, and mitochondrial membrane potential disruption. Mechanistically, H₂O₂ increased both LC3-II and p62 levels, indicating impaired autophagic flux. Activation of autophagy by serum starvation alleviated H₂O₂-induced injury, whereas chloroquine exacerbated cellular damage and abolished the protective effects of BSA-MnO₂ NPs, suggesting that the restoration of autophagy contributes to BSA-MnO₂ NPs-mediated neuroprotection. Further analysis showed that BSA-MnO₂ NPs enhanced Akt phosphorylation, while LY294002, a PI3K inhibitor, suppressed Akt activation, disrupted autophagy regulation, and eliminated their neuroprotective effects. In contrast, chloroquine did not affect Akt phosphorylation, indicating that PI3K/Akt signaling acts upstream of autophagy regulation. Conclusions: Collectively, these findings demonstrate that BSA-MnO₂ NPs protect PC12 cells against H₂O₂-induced oxidative injury by restoring autophagy through the PI3K/Akt signaling pathway, highlighting a potential role of BSA-MnO₂ NPs in the treatment of oxidative-stress-related neurodegenerative disorders.