Comparative effects of transforming growth factor beta isoforms on redox metabolism in thyroid cells

Introduction: Transforming growth factor beta (TGF-beta) regulates thyroid function and growth. However, tumoral thyroid cells became resistant to this factor as they undifferentiated. Little is known about the effects of TGF-beta isoforms. We compared the role of redox metabolism in the response to TGF-beta isoforms between non tumoral and tumoral thyroid cells. Methodology and results: Differentiated rat thyroid cells (FRTL-5) and human thyroid follicular carcinoma cells (WRO) were treated with the three isoforms of TGF-beta. TGF-beta isoforms stopped cell cycle at different steps; G1 for FRTL-5 and G2/M for WRO. The three isoforms decreased cell viability and increased ROS accumulation in both cell lines. These effects were more pronounced in FRTL-5 than in WRO, and the isoform beta 1 was more potent in ROS production than the other two. TGF-beta isoforms decreased total glutathione, catalase expression and it activity in both cell lines. Only in FRTL-5 the lipid peroxidation was demonstrated. Moreover, TGF-beta 1 decreased glutathione peroxidase and mitochondrial superoxide dismutase mRNA expression and increased mitochondrial ROS in FRTL-5, but no in WRO. Pretreatment with selenium increased glutathione peroxidase activity and decreased ROS production in WRO treated with TGF-beta isoforms. Furthermore, selenium partially reversed the effect of TGF-beta isoforms on cell viability only in WRO cells. The knockdown of endogenous NOX4 significantly reduced the TGF-beta 1 effect on cell viability in WRO but no in FRTL-5. Conclusion: TGF-beta disrupted the redox balance and increased ROS accumulation in both cell lines. FRTL5 cells showed reduced antioxidant capacity and had a greater sensitivity to TGF-beta isoforms, while WRO cells were more resistant. This observation provides new insights into the potential role of TGF-beta in the redox regulation of thyroid cells. (C) 2017 Elsevier B.V. All rights reserved.