Emodin Protects SH-SY5Y Cells Against Zinc-Induced Synaptic Impairment and Oxidative Stress Through ERK1/2 Pathway

Background: Zinc is an essential trace element important for the physiological function of the central nervous system. The abnormal accumulation of zinc inside neurons may induce mitochondrial dysfunction and oxidative stress which contributes to many brain diseases. We hypothesized that natural anthraquinone derivative emodin can protect against neurotoxicity induced by pathological concentrations of zinc via Extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway, and alleviate the oxidative stress and mitochondria dysfunction. Results: : Human neuroblastoma (SH-SY5Y cells) was treated with zinc sulfate and different concentrations of emodin, and was examined in the changes in the levels of ERK1/2 expressions, oxidative stress (DCFH-DA staining), mitochondrial function (JC-1 staining), and lipid peroxidation (4-hydroxynonenal staining), and DNA oxidation (8-Hydroxy-2-deoxyguanosine staining). Emodin ameliorated zinc-induced altered expression level of phosphorylated-ERK1/2 (not total-ERK1/2), and synaptic proteins (presynaptic SNAP25, synaptophysin and postsynaptic PSD95) in SH-SY5Y cells, in a dose-dependent manor. Moreover, emodin inhibited the generation of reactive oxygen substrates, oxidative stress, facilitated the collapse of mitochondrial membrane potential (ΔΨm) in SH-SY5Y cells. Conclusion: Our results indicated that emodin exerts neuroprotective effects against zinc by normalizing synaptic impairment via decreasing the phosphorylation of ERK1/2, reducing reactive oxygen substrates and protecting mitochondrial function.