ECEESPE2025 Rapid Communications Rapid Communications 11: Thyroid Part 1 (6 abstracts)
The role of ferroptosis as a novel alternative cell death model in thyrocytes from Hashimotós thyroiditis patients
Pablo Sacristán-Gómez 1 , Susana Delgado-Martín 2 , Ana Serrano-Somavilla 1 , Sánchez de la Blanca Carrero Nuria 1 , Andrea Álvarez-Rodríguez 1 , Jose Luis Muñoz de Nova 3 , Miguel Antonio Sampedro-Nuñez 1 , Antonio Martínez-Ruiz 2 , Monica Marazuela 1 & Rebeca Martínez-Hernández 1
1Instituto de Investigación Sanitaria la Princesa (IIS-IP), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER GCV14/ER/12), Endocrinología, Madrid, Spain; 2Instituto de Investigación Sanitaria la Princesa (IIS-IP), Hospital Santa Cristina, Unidad de Investigación, Madrid, Spain; 3Instituto de Investigación Sanitaria la Princesa (IIS-IP), Cirugía General y Digestiva, Madrid, Spain
JOINT1029
Introduction: Autoimmune thyroid disorders (AITD) are organ-specific diseases that result from the dysregulation of the immune system homeostasis, leading to an immune response against self-thyroid antigens. The main AITD are Hashimotós thyroiditis (HT) and Graves´ disease (GD). Ferroptosis is an intracellular iron-dependent form of cell death that involves the generation of reactive oxygen species, which increases oxidative stress and lipid peroxidation. Glutathione peroxidase 4 (GPX4) has a key role in reducing lipid peroxides into lipid alcohols, preventing ferroptosis. The high oxidative stress and the thyroid folicular cells (TFCs) death that takes places in HT patients suggests that ferroptosis could represent an alternative cell death pathway in HT pathogenesis.
Methodology: We analyzed lipid peroxidation with a sensor for lipid peroxidation (BodipyTM 581/591 C11) in a human thyroid follicular cell line stimulated with HT-associated proinflammatory cytokines (IFN-γ and TNF-α), ferroptosis inductors (RSL3 and erastin) and inhibitors (ferrostatin-1). At the same time, we evaluated cell death with the 7-AAD Staining Solution. We evaluated the levels of ferrous ion (Fe2+), a ferroptosis inductor, in cellular models with an iron sensing dye (FerroOrange). We measured the expression of GPX4 and lipid peroxidation products, such as 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) in thyroid tissue and in vitro models by Western Blot (WB) and image.
Results: We observed an increase of lipid peroxidation and cell death in thyrocytes stimulated with IFN-γ and TNF-α. This increase was similar with the ferroptosis inductors RSL3 and erastin and, interestingly, this effect was reverted by ferrostatin-1. Furthermore, IFN-γ and TNF-α decreased GPX4 expression and increased Fe2+ levels. In thyroid tissue, GPX4 expression was downregulated in TFCs from HT patients compared to controls or GD. Although MDA expression did not change between conditions, the levels of 4-HNE, a lipid peroxidation product, were increased in HT, suggesting a relationship between ferroptosis and HT pathogenesis.
Conclusions: Our data indicates that ferroptosis may constitute a novel alternative cell death model in HT pathogenesis because of the proinflammatory microenvironment.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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