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

Romina Oglio1, Lisa Thomasz2, Leonardo Salvarredi1

  • 1Nuclear Biochemistry Division, Argentine National Atomic Energy Commission, Buenos Aires 1429, Argentina.

Abstract

Insights

Transforming growth factor beta (TGF-β) disrupts redox balance in thyroid cells, increasing reactive oxygen species (ROS). Differentiated cells are more sensitive to TGF-β than tumoral cells, highlighting redox metabolism

Area of Science:

  • Endocrinology
  • Cell Biology
  • Biochemistry

Background:

  • Transforming growth factor beta (TGF-β) is crucial for thyroid function and growth.
  • Tumoral thyroid cells often develop resistance to TGF-β.
  • The specific roles of different TGF-β isoforms in thyroid cell redox metabolism are not well understood.

Purpose of the Study:

  • To compare the effects of TGF-β isoforms on redox metabolism in non-tumoral (FRTL-5) and tumoral (WRO) thyroid cells.
  • To investigate the differential responses of these cell types to TGF-β-induced oxidative stress.

Main Methods:

  • Treatment of FRTL-5 and WRO cells with TGF-β isoforms.
  • Assessment of cell cycle progression, viability, and reactive oxygen species (ROS) accumulation.
  • Measurement of antioxidant markers including glutathione and catalase.
  • Analysis of specific enzyme expression (glutathione peroxidase, superoxide dismutase) and lipid peroxidation.
  • Intervention with selenium and NOX4 knockdown.

Main Results:

  • TGF-β isoforms induced cell cycle arrest (G1 in FRTL-5, G2/M in WRO) and decreased viability in both cell lines.
  • ROS accumulation and disruption of redox balance were observed in both cell types, with greater impact on FRTL-5 cells.
  • TGF-β isoform β1 showed higher potency in ROS production.
  • Antioxidant capacity was reduced in FRTL-5 cells, making them more sensitive.
  • Selenium pretreatment mitigated ROS and partially restored viability in WRO cells.
  • NOX4 knockdown affected TGF-β1's impact on WRO cell viability.

Conclusions:

  • TGF-β isoforms significantly disrupt the redox balance in thyroid cells, leading to increased ROS.
  • Differentiated thyroid cells (FRTL-5) exhibit reduced antioxidant capacity and higher sensitivity to TGF-β compared to tumoral cells (WRO).
  • These findings offer new insights into TGF-β's role in thyroid cell redox regulation and potential therapeutic targets.

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