Journal: Journal of Molecular Neuroscience
Article Title: Docosahexaenoic Acid Modulates Autophagy and Confers Neuronal Resilience under Hypoxia–Reoxygenation Stress
doi: 10.1007/s12031-026-02512-1
Figure Lengend Snippet: Proposed mechanism of DHA-induced neuroprotection under hypoxia–reoxygenation stress. Hypoxia exacerbates neuronal injury by impairing oxidative phosphorylation and triggering oxidative stress, apoptosis, and suppression of autophagy. In this study, nerve growth factor-differentiated PC12 (NGFDPC12) cells exposed to 0.5% O₂ showed increased expression of the stress-response genes HIF-1α and BNIP3 , accumulation of reactive oxygen species (ROS), and upregulation of the oxidative stress marker FABP5 . Pretreatment with docosahexaenoic acid (DHA) or the autophagy activator rapamycin markedly improved cell viability and reduced apoptosis. DHA restored the expression of autophagy-related genes ( Atg5 , Atg7 , Atg12 ) suppressed by hypoxia and increased Beclin-1 phosphorylation and LC3 lipidation, consistent with enhanced autophagic activity. Together, these findings support a model in which DHA pretreatment induces mild ROS signaling that activates the AMPK–Beclin-1–LC3 pathway, promoting autophagy and reducing oxidative stress and apoptosis under hypoxia–reoxygenation stress. The illustration was generated with BioRender.com
Article Snippet: Membranes were blocked with Intercept blocking buffer (Li-Cor Biotechnology, Lincoln, NE) and incubated overnight at 4 °C with primary antibodies against LC3A/B (Cat# 4108 S, CST) and phospho-Ser93-Beclin-1 (Cat# 14717 S, CST) and total Beclin-1 (Cat# 3495 S, CST).
Techniques: Phospho-proteomics, Expressing, Marker, Activity Assay, Generated
