Regulation of the cellular redox state and the expression of DNA methyltransferase-1 in peripheral blood mononuclear cells from patients with Graves’ disease

COSTILLA, MELISA; CURRIA, MARINA INÉS; KLECHA, ALICIA JUANA; CREMASCHI, GRACIELA; SABAN, MELINA; DI CUGNO, MARIANA; BARREIRO ARCOS, MARÍA LAURA

Endocrinología, Diabetes y Nutrición

Elsevier España

Lugar: Barcelona; Año: 2021

2530-0164

Background: Graves? disease is an autoimmune disorder characterised by excessive productionof thyroid hormones, which induces increased cellular metabolism in most tissues and increasedproduction of reactive oxygen species (ROS). The aim of this work was to analyse the effectof ROS on cell viability and the expression of catalase (CAT), glutathione peroxidase-1 (GPx1), superoxide dismutase (SOD-1) and DNA methyltransferase-1 (DNMT-1) in peripheral bloodmononuclear cells (PBMC) from patients with newly diagnosed Graves? disease or treated withmethimazole. Patients and methods: For this study, women patients with newly diagnosed Graves? disease (n = 18), treated with methimazole (n = 6) and healthy subjects (n = 15) were recruited. ROSwere evaluated by flow cytometry, and the viability/apoptosis of PBMC was analysed by flowcytometry and fluorescence microscopy. Genomic expression of CAT, GPx-1, SOD-1 and DNMT-1was quantified by real-time PCR. Results: We found high levels of ROS and increased expression of CAT, GPx-1, SOD-1 and DNMT-1 in PBMC from patients with newly diagnosed Graves? disease. Methimazole treatment reversed these parameters. Cell viability was similar in all study groups. Conclusions: ROS induces the expression of CAT, GPx-1, and SOD-1. The activity of theseenzymes may contribute to the protection of PBMC from the harmful effect of free radicalson cell viability. Increased expression of DNMT-1 may be associated with aberrant methylationpatterns in immunoregulatory genes contributing to autoimmunity in Graves? disease.