Resveratrol Protects SH-SY5Y Cells Against Oleic Acid-Induced Glucolipid Metabolic Dysfunction and Cell Injuries Via the Wnt/β-Catenin Signalling Pathway.

Abstract

Resveratrol (RES) is a polyphenol with diverse beneficial biological and pharmacological activities, and our previous results have demonstrated its neuroprotective effects in several metabolic diseases, including non-alcoholic fatty liver disease. The aim of the present study is to investigate the potential effect of RES against oleic acid (OA)-induced cell injuries in SH-SY5Y cells and explore the possible mechanism. Based on the dose- and time-dependent effects of OA on cell proliferation and LDH release, SH-SY5Y cells were challenged with OA and incubated with or without RES (10-5-10-9 mM) or sitagliptin (STG, 10-7 mM). Lipid accumulation, SREBP1 and PPARα protein expression, glucose consumption and IRS1, AKT, ERK phosphorylation under insulin stimulation, and ROS production were detected. The protein expression of brain-derived neurotrophic factor (BDNF), Copine 6, and key molecules in the Wnt/β-catenin signalling pathway were measured via western blot. The expression of Wnt 1 was also measured via immunofluorescence staining. The results showed that RES treatment could alleviate the neurotoxicity induced by OA, as indicated by the increased cell proliferation and the decreased concentration of LDH in the supernatant. The increased lipid deposition and protein expression of SREBP1 and PPARα induced by OA was also reversed by treatment with RES. Moreover, RES could upregulate glucose consumption and the protein expression of phosphorylated IRS1, AKT, ERK and reduced ROS production in OA-induced SH-SY5Y cells. Furthermore, RES treatment reversed the imbalanced protein expression of BDNF, Copine 6, p-β-catenin, and Wnt 1 in SH-SY5Y cells induced by OA and decreased the hyperexpression of p-GSK3β. However, these effects were suppressed by DKK1, which is a specific antagonist of the Wnt signalling pathway. These results suggested that RES has a neuroprotective effect against OA-induced cell injury and dysfunctional glucolipid metabolism, and the mechanism might involve its ability to regulate oxidative stress and insulin resistance via the Wnt/β-catenin signalling pathway.

• Authors: Jing-Xian Xu, Ke Fang, Xin-Ran Gao, Sen Liu, Jin-Fang Ge
• Journal: Neurochemical research (Neurochem Res) Vol. 46 Issue 11 Pg. 2936-2947 (Nov 2021) ISSN: 1573-6903 [Electronic] United States
• PMID: 34260003 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• DKK1 protein, human
• Intercellular Signaling Peptides and Proteins
• Neuroprotective Agents
• Oleic Acid
• Glucose
• Resveratrol

Topics

• Cell Line, Tumor
• Cell Proliferation (drug effects, physiology)
• Dose-Response Relationship, Drug
• Glucose (metabolism)
• Humans
• Intercellular Signaling Peptides and Proteins (pharmacology)
• Lipid Metabolism (drug effects, physiology)
• Neuroprotective Agents (pharmacology)
• Oleic Acid (toxicity)
• Oxidative Stress (drug effects, physiology)
• Resveratrol (pharmacology)
• Wnt Signaling Pathway (drug effects, physiology)