The Protective Effect of Docosahexaenoic Acid on PC12 Cells in Oxidative Stress Induced by H2O2 through the TrkB-Erk1/2-CREB Pathway

Abstract

Docosahexaenoic acid (DHA) has attracted plenty of interest in the prevention of neurodegenerative diseases. Although the beneficial effects of DHA on the central nervous system function are recognized, more information on the molecular mechanisms involved in its neuroprotective effects is required. The present study aimed to evaluate the effects of DHA on the function of mitochondria, neurite growth-related proteins signaling pathway, and neural signal transmission. In this study, PC12 cells were treated with H2O2 (400 μM) to establish an oxidative damage model. Results showed that DHA improved the viability and morphology of PC12 cells. DHA significantly increased the antioxidant capacity, mitochondrial membrane potential, and activity of ATPase in the cells. Furthermore, the phosphorylation levels of tyrosine kinase receptor (BTrkB), phospholipase C-γ1 (PLCγ1), calcium/calmodulin-dependent protein kinase II (CaMKII), extracellular regulated protein kinases 1/2 (ERK1/2), and cAMP-response element-binding protein (CREB) were upregulated by DHA. The damage on F-actin induced by H2O2 was reversed by DHA, indicating that DHA could protect neurite outgrowth. In addition, DHA increased the content of acetylcholine and γ-aminobutyric acid while decreasing glutamic acid. These results revealed that DHA could protect PC12 cells from damage induced by H2O2 through the TrkB-ERK1/2-CREB pathway.