Selenium bioavailability modulates the sensitivity of thyroid cells to iodide excess

Area of Science:

• Endocrinology
• Molecular Biology
• Nutritional Science

Background:

• Iodide is crucial for thyroid hormone synthesis; imbalances cause thyroid pathologies.
• Selenium (Se) is essential for thyroid health, regulating redox homeostasis.
• Excess iodide downregulates sodium-iodide-symporter (NIS), an effect reversed by Se supplementation.
• NOX4-derived reactive oxygen species (ROS) are implicated in iodide-induced NIS repression.

Purpose of the Study:

• To investigate the role of Se bioavailability in modulating thyroid cell response to excess iodide.
• To explore the mechanisms by which Se influences iodide-induced changes in thyroid cells (FRTL-5).

Main Methods:

• Utilized differentiated rat thyroid cell line (FRTL-5).
• Employed siRNA-mediated silencing of Nox4.
• Assessed mRNA expression of various genes (TGF-β1, GPX1, TXRND1, PTP1B, PTEN, NIS).
• Measured reactive oxygen species (ROS) levels, Nrf2 transcriptional activity, and AKT phosphorylation.
• Investigated the effects of 2-α-iodohexadecanal (2-IHD) and its inhibitor (SB431542).

Main Results:

• Se supplementation reversed iodide-induced increases in TGF-β1, AKT phosphorylation, and ROS levels, while restoring GPX1 and TXRND1 expression.
• Iodide induced Nrf2 activity and selenoenzyme response only in Se-supplemented cells; Se inhibited NF-κB phosphorylation.
• Iodide excess decreased phosphatase activity and PTEN/PTP1B expression; Se restored PTEN expression.
• 2-IHD reduced NIS expression via a ROS-independent mechanism involving TGF-β1 signaling, an effect partially mitigated by Se.

Conclusions:

• Se bioavailability enhances antioxidant gene expression via Nrf2 activation.
• Se modulates PI3K/AKT signaling and NIS expression through redox mechanisms.
• Se plays a protective role against iodide excess by influencing key cellular pathways.