Oxidative stress and dietary micronutrient deficiencies contribute to overexpression of epigenetically regulated genes by lupus T cells
Autor: | Faith M. Strickland, Bruce C. Richardson, Donna Ray |
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Rok vydání: | 2018 |
Předmět: |
CD4-Positive T-Lymphocytes
Male 0301 basic medicine Riboflavin T-Lymphocytes Choline Epigenesis Genetic chemistry.chemical_compound Methionine 0302 clinical medicine Lupus Erythematosus Systemic Immunology and Allergy Micronutrients DNA Modification Methylases Homocysteine Systemic lupus erythematosus Methylation Middle Aged Flow Cytometry Vitamin B 12 Zinc medicine.anatomical_structure DNA methylation Female Peroxynitrite Adult T cell Immunology DNA methyltransferase Article Young Adult 03 medical and health sciences Folic Acid Peroxynitrous Acid medicine Humans Aged 030203 arthritis & rheumatology DNA Methylation medicine.disease Molecular biology Vitamin B 6 Diet Oxidative Stress 030104 developmental biology Gene Expression Regulation chemistry Case-Control Studies Transmethylation |
Zdroj: | Clinical Immunology. 196:97-102 |
ISSN: | 1521-6616 |
DOI: | 10.1016/j.clim.2018.04.003 |
Popis: | Patients with active lupus have altered T cells characterized by low DNA methyltransferase levels. We hypothesized that low DNA methyltransferase levels synergize with low methionine levels to cause greater overexpression of genes normally suppressed by DNA methylation. CD4+ T cells from lupus patients and controls were stimulated with PHA then cultured in custom media with normal or low methionine levels. Oxidative stress was induced by treating the normal CD4+ T cells with peroxynitrite prior to culture. Methylation sensitive gene expression was measured by flow cytometry. Results showed low methionine levels caused greater overexpression of methylation sensitive genes in peroxynitrite treated T cells relative to untreated T cells, and in T cells from lupus patients relative to T cells from healthy controls. In conclusion, low dietary transmethylation micronutrient levels and low DNA methyltransferase levels caused either by oxidative stress or lupus, have additive effects on methylation sensitive T cell gene expression. |
Databáze: | OpenAIRE |
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