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

Qian Chen; Chencen Lai; Fa Chen; Yuanting Ding; Yiyuan Zhou; Songbai Su; Ruiqing Ni; Zhi Tang

doi:10.3389/fphar.2022.821521

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

Front Pharmacol. 2022 Feb 7:13:821521. doi: 10.3389/fphar.2022.821521. eCollection 2022.

Authors

Qian Chen^{1

2}, Chencen Lai³, Fa Chen^{2

4}, Yuanting Ding², Yiyuan Zhou¹, Songbai Su³, Ruiqing Ni^{5

6}, Zhi Tang^{2

7}

Affiliations

¹ Department of Obstetrics, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China.
² Clinical Research Center, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China.
³ Preparation Center, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China.
⁴ Department of Miao Medicine, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China.
⁵ Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland.
⁶ Institute for Biomedical Engineering, ETH Zurich and University of Zurich, Zurich, Switzerland.
⁷ Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education and Key Laboratory of Medical Molecular Biology of Guizhou Province, Guizhou Medical University, Guiyang, China.

Abstract

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 contribute to many brain diseases. We hypothesized that natural anthraquinone derivative emodin can protect against neurotoxicity induced by pathological concentrations of zinc via the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and alleviate oxidative stress and mitochondrial dysfunction. Human neuroblastoma (SH-SY5Y 26 cells) was treated with zinc sulfate and different concentrations of emodin, and changes in the levels of ETK1/2 expression, oxidative stress (DCFH-DA staining), mitochondrial function (JC-1 staining), lipid peroxidation (4-hydroxynonenal staining), and DNA oxidation (8-hydroxy-2-deoxyguanosine staining) were examined. Emodin ameliorated zinc-induced altered expression of levels of phosphorylated ERK1/2 (not total ETK1/2) and synaptic proteins (presynaptic SNAP 25, synaptophysin and postsynaptic PSD95) in SH-SY5Y cells. Moreover, emodin inhibited the generation of reactive oxygen species and oxidative stress and facilitated the collapse of mitochondrial membrane potential (ΔΨm) in SH-SY5Y cells. In conclusion, our results indicated that emodin exerts neuroprotective effects against zinc by normalizing synaptic impairment by decreasing the phosphorylation of ERK1/2, reducing reactive oxygen species and protecting mitochondrial function.

Keywords: ERK1/2 pathway; SH-SY5Y cells; emodin; mitochondria; oxidative stress; synaptic impairment; zinc.