Regulation of the cellular redox state and the expression of DNA methyltransferase-1 in peripheral blood mononuclear cells from patients with Graves’ disease
Abstract: Background: Graves’ disease is an autoimmune disorder characterised by excessive production of thyroid hormones, which induces increased cellular metabolism in most tissues and increased production of reactive oxygen species (ROS). The aim of this work was to analyse the effect of 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 blood mononuclear cells (PBMC) from patients with newly diagnosed Graves’ disease or treated with methimazole. 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. ROS were evaluated by flow cytometry, and the viability/apoptosis of PBMC was analysed by flow cytometry and fluorescence microscopy. Genomic expression of CAT, GPx-1, SOD-1 and DNMT-1 was 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 these enzymes may contribute to the protection of PBMC from the harmful effect of free radicals on cell viability. Increased expression of DNMT-1 may be associated with aberrant methylation patterns in immunoregulatory genes contributing to autoimmunity in Graves’ disease.
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Elsevier
2021
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| Subjects: | ENFERMEDAD DE GRAVES, CELULAS MONONUCLEARES DE SANGRE PERIFÉRICA, ESTRES OXIDATIVO, ENZIMAS ANTIOXIDANTES, ADN METILTRANSFERASA-1, |
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ENFERMEDAD DE GRAVES CELULAS MONONUCLEARES DE SANGRE PERIFÉRICA ESTRES OXIDATIVO ENZIMAS ANTIOXIDANTES ADN METILTRANSFERASA-1 ENFERMEDAD DE GRAVES CELULAS MONONUCLEARES DE SANGRE PERIFÉRICA ESTRES OXIDATIVO ENZIMAS ANTIOXIDANTES ADN METILTRANSFERASA-1 |
| spellingShingle |
ENFERMEDAD DE GRAVES CELULAS MONONUCLEARES DE SANGRE PERIFÉRICA ESTRES OXIDATIVO ENZIMAS ANTIOXIDANTES ADN METILTRANSFERASA-1 ENFERMEDAD DE GRAVES CELULAS MONONUCLEARES DE SANGRE PERIFÉRICA ESTRES OXIDATIVO ENZIMAS ANTIOXIDANTES ADN METILTRANSFERASA-1 Saban, Melina Costilla, Melisa Klecha, Alicia Juana Di Cugno, Mariana Curriá, Marina Inés Cremaschi, Graciela A. Barreiro Arcos, María Laura Regulation of the cellular redox state and the expression of DNA methyltransferase-1 in peripheral blood mononuclear cells from patients with Graves’ disease |
| description |
Abstract:
Background: Graves’ disease is an autoimmune disorder characterised by excessive production
of thyroid hormones, which induces increased cellular metabolism in most tissues and increased
production of reactive oxygen species (ROS). The aim of this work was to analyse the effect
of 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 blood
mononuclear cells (PBMC) from patients with newly diagnosed Graves’ disease or treated with
methimazole.
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. ROS
were evaluated by flow cytometry, and the viability/apoptosis of PBMC was analysed by flow
cytometry and fluorescence microscopy. Genomic expression of CAT, GPx-1, SOD-1 and DNMT-1
was 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 these
enzymes may contribute to the protection of PBMC from the harmful effect of free radicals
on cell viability. Increased expression of DNMT-1 may be associated with aberrant methylation
patterns in immunoregulatory genes contributing to autoimmunity in Graves’ disease. |
| format |
Artículo |
| topic_facet |
ENFERMEDAD DE GRAVES CELULAS MONONUCLEARES DE SANGRE PERIFÉRICA ESTRES OXIDATIVO ENZIMAS ANTIOXIDANTES ADN METILTRANSFERASA-1 |
| author |
Saban, Melina Costilla, Melisa Klecha, Alicia Juana Di Cugno, Mariana Curriá, Marina Inés Cremaschi, Graciela A. Barreiro Arcos, María Laura |
| author_facet |
Saban, Melina Costilla, Melisa Klecha, Alicia Juana Di Cugno, Mariana Curriá, Marina Inés Cremaschi, Graciela A. Barreiro Arcos, María Laura |
| author_sort |
Saban, Melina |
| title |
Regulation of the cellular redox state and the expression of DNA methyltransferase-1 in peripheral blood mononuclear cells from patients with Graves’ disease |
| title_short |
Regulation of the cellular redox state and the expression of DNA methyltransferase-1 in peripheral blood mononuclear cells from patients with Graves’ disease |
| title_full |
Regulation of the cellular redox state and the expression of DNA methyltransferase-1 in peripheral blood mononuclear cells from patients with Graves’ disease |
| title_fullStr |
Regulation of the cellular redox state and the expression of DNA methyltransferase-1 in peripheral blood mononuclear cells from patients with Graves’ disease |
| title_full_unstemmed |
Regulation of the cellular redox state and the expression of DNA methyltransferase-1 in peripheral blood mononuclear cells from patients with Graves’ disease |
| title_sort |
regulation of the cellular redox state and the expression of dna methyltransferase-1 in peripheral blood mononuclear cells from patients with graves’ disease |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://repositorio.uca.edu.ar/handle/123456789/14017 |
| work_keys_str_mv |
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| spelling |
oai:ucacris:123456789-140172022-05-25T05:00:53Z Regulation of the cellular redox state and the expression of DNA methyltransferase-1 in peripheral blood mononuclear cells from patients with Graves’ disease Regulación del estado redox celular y la expresión de ADN metiltransferasa-1 en células mononucleares de sangre periférica de pacientes con enfermedad de Graves Saban, Melina Costilla, Melisa Klecha, Alicia Juana Di Cugno, Mariana Curriá, Marina Inés Cremaschi, Graciela A. Barreiro Arcos, María Laura ENFERMEDAD DE GRAVES CELULAS MONONUCLEARES DE SANGRE PERIFÉRICA ESTRES OXIDATIVO ENZIMAS ANTIOXIDANTES ADN METILTRANSFERASA-1 Abstract: Background: Graves’ disease is an autoimmune disorder characterised by excessive production of thyroid hormones, which induces increased cellular metabolism in most tissues and increased production of reactive oxygen species (ROS). The aim of this work was to analyse the effect of 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 blood mononuclear cells (PBMC) from patients with newly diagnosed Graves’ disease or treated with methimazole. 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. ROS were evaluated by flow cytometry, and the viability/apoptosis of PBMC was analysed by flow cytometry and fluorescence microscopy. Genomic expression of CAT, GPx-1, SOD-1 and DNMT-1 was 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 these enzymes may contribute to the protection of PBMC from the harmful effect of free radicals on cell viability. Increased expression of DNMT-1 may be associated with aberrant methylation patterns in immunoregulatory genes contributing to autoimmunity in Graves’ disease. Resumen: Antecedentes: La enfermedad de Graves es un trastorno autoinmune caracterizado por una producción excesiva de hormonas tiroideas, que induce un aumento del metabolismo celular en la mayoría de los tejidos y una mayor producción de especies reactivas de oxígeno (ROS). El objetivo de este trabajo fue analizar el efecto de las ROS sobre la viabilidad celular y la expresión de catalasa (CAT), glutatión peroxidasa-1 (GPx-1), superóxido dismutasa (SOD-1) y ADN metiltransferasa-1 (DNMT-1) en células mononucleares de sangre periférica (PBMC) de pacientes con enfermedad de Graves recién diagnosticada o tratados con metimazol. Pacientes y métodos: Se seleccionó a mujeres con enfermedad de Graves recién diagnosticada (n = 18), tratadas con metimazol (n = 6) y a sujetos sanos (n = 15). La producción de ROS fue evaluada por citometría de flujo. La viabilidad y apoptosis de las PBMC fue analizada por citometría de flujo y microscopía de fluorescencia. La expresión genómica de CAT, GPx-1, SOD-1 y DNMT-1 fue cuantificada por PCR en tiempo real. Resultados: Encontramos altos niveles de ROS y una mayor expresión de CAT, GPx-1, SOD-1 y DNMT-1 en PBMC de pacientes con enfermedad de Graves recién diagnosticada. El tratamiento con metimazol revirtió estos parámetros. La viabilidad celular fue similar en todos los grupos de estudio. Conclusiones: Las ROS inducen la expresión de CAT, GPx-1 y SOD-1. La actividad de estas enzimas podría contribuir a la protección de las PBMC del efecto nocivo de los radicales libres sobre la viabilidad celular. El aumento de la expresión de DNMT-1 podría estar asociado con patrones de metilación aberrantes en genes inmunorreguladores que contribuyen a la autoinmunidad en la enfermedad de Graves. 2022-05-24T12:05:49Z 2022-05-24T12:05:49Z 2021 Artículo Saban, M. et al. Regulation of the cellular redox state and the expression of DNA methyltransferase-1 in peripheral blood mononuclear cells from patients with Graves’ disease [en línea]. Endocrinología, Diabetes y Nutrición. 2021. doi: https://doi.org/10.1016/j.endinu.2021.07.011. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/14017 2530-0164 (online) https://repositorio.uca.edu.ar/handle/123456789/14017 10.1016/j.endinu.2021.07.011 eng Mecanismos epigenéticos involucrados en la funcionalidad del sistema inmune en pacientes con hipertiroidismo de graves. Participación del estrés oxidativo Acceso abierto http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Elsevier Endocrinología, Diabetes y Nutrición, 2021 |