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

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.