Induction of epigenetic mechanisms associated to oxidative stress in patients with Graves? Hyperthyroidism.

MACRI DELBONO R.; COSTILLA M.; KLECHA A ; SABAN M.; CURRIA M.; DI CUGNEO M, ; CREMASCHI G.; BARREIRO ARCOS M. L.

Buenos Aires

Congreso; III International Congress in Translational Medicine; 2016

Albert-Ludwigs University of Freiburg (Alemania) junto con la Universidad de Buenos Aires.

Graves pathology is an autoimmune disease characterized by humoral hyper-reactivity against thyroid autoantigens leading to the state of hyperthyroidism in individuals. The aim of this work was to study the presence of epigenetic mechanisms in peripheral blood mononuclear cells (PBMC) of patients with Graves´ disease, and analyze the involvement of oxidative stress in the induction of these mechanisms. To this end, the PBMC of patients with Graves disease (n = 8 individuals) and healthy controls (n = 10 individuals) were purified from peripheral blood using Ficoll-Hypaque and was analyzed the levels of reactive oxygen species (ROS), antioxidant enzymes, the expression of DNA methyltransferase (DNMT) and histone modifications. We have observed a significant increase of ROS in PBMC of patients with Graves? disease that was correlated with the increase in the activity and genomic expression of the Catalase and Glutatión Peroxidasa-1 enzymes. Treatment of PBMC with an oxidative stress inducer (H2O2) showed a greater ability to detoxification of peroxides and a lower level of apoptosis in individuals with Graves´ disease. We found a significant increase in the genomic and protein expression of DNMT in patients with Graves´ disease which was accompanied by an increase in the levels of histone hypoacetylation.These results allow us to infer that oxidative stress may induce epigenetic changes such as DNA methylation and histone hypoacetylation, which could affect gene transcription in lymphocyte cells involved in control of the immune response, contributing to the phenomenon of autoimmunity and to the pathogenesis of Graves´ disease.