Reciprocal regulation of glycogen synthase kinase-3 and β-catenin affects cell proliferation of fructose treated rat hepatocytes

Year 2022, Volume: 2 Issue: 2, 91 - 99, 24.04.2022

Aykut Bostancı Gökhan Sadi

Abstract

High consumption of fructose might lead to obesity, diabetes, and metabolic syndrome in the long term. Recent studies demonstrated the induction of insulin resistance in the liver tissues by down-regulation of insulin signaling pathway elements. Glycogen synthase kinase-3 (GSK-3), one of the insulin signaling elements, suppresses the β-catenin function that is required for cell proliferation and integrity. This study is designed to demonstrate the effects of fructose on the proliferation of rat hepatocytes and its effects on GSK-3 and β-catenin expression. Accordingly, rat hepatocytes were treated with different concentrations of fructose, and cell proliferation was followed with an xCELLigence real-time cell analysis system. Besides, gene and protein expression levels of GSK-3β and β-catenin were evaluated in fructose-treated cells with qRT-PCR and Western blot, respectively. The results demonstrated proliferative effects of fructose at low doses (0-25-50 mM), but cytotoxic properties are pronounced at higher doses (100-150 mM). The IC50 value was calculated as 140±7 mM fructose for Clone-9 cells. Molecular effects of fructose over GSK-3β and β-catenin appeared at gene and protein levels at 100- and 150-mM concentrations at which GSK-3β were suppressed. Conversely, high-dose fructose leads to β-catenin induction as a compensatory mechanism to counteract the antiproliferative effects of fructose at these doses. In conclusion, high-dose fructose-induced cytotoxicity activates a compensatory molecular mechanism involving β-catenin induction which might protect the cells in the long-term fructose exposure. Keywords: Fructose, cytotoxicity, GSK-3β, β-catenin, gene expressionVolume: 2Issue: 22022E-ISSN: 2791-6022https://journals.gen.tr/jspReceived: 2021-03-08Accepted: 2022-03-24ORIGINAL ARTICLEThis work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords

Fructose, cytotoxicity, GSK-3β, β-catenin, gene expression

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