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

Aykut Bostancı; Gökhan Sadi

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

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

Kaynakça

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Ayrıntılar

Birincil Dil

İngilizce

Konular

Sağlık Kurumları Yönetimi

Bölüm

Araştırma Makalesi

Yazarlar

Aykut Bostancı Bu kişi benim
0000-0002-6855-0645
Türkiye

Gökhan Sadi Bu kişi benim
0000-0002-6422-1203
Türkiye

Yayımlanma Tarihi

24 Nisan 2022

Gönderilme Tarihi

8 Mart 2021

Kabul Tarihi

24 Mart 2022

Yayımlandığı Sayı

Yıl 2022 Cilt: 2 Sayı: 2

IZ

https://izlik.org/JA82BL97HZ

Kaynak Göster

RIS / Bibtex

Vancouver

1.Aykut Bostancı, Gökhan Sadi. Reciprocal regulation of glycogen synthase kinase-3 and β-catenin affects cell proliferation of fructose treated rat hepatocytes. Health Sci. Q. [Internet]. 01 Nisan 2022;2(2):91-9. Erişim adresi: https://izlik.org/JA82BL97HZ