دورية أكاديمية
Oxidative Stress-Induced Sirtuin1 Downregulation Correlates to HIF-1α, GLUT-1, and VEGF-A Upregulation in Th1 Autoimmune Hashimoto's Thyroiditis.
| العنوان: | Oxidative Stress-Induced Sirtuin1 Downregulation Correlates to HIF-1α, GLUT-1, and VEGF-A Upregulation in Th1 Autoimmune Hashimoto's Thyroiditis. |
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| المؤلفون: | Hepp, Michael, Wérion, Alexis, De Greef, Axel, de Ville de Goyet, Christine, de Bournonville, Marc, Behets Wydemans, Catherine, Lengele, Benoit, Daumerie, Chantal, Mourad, Michel, Ludgate, Marian, Many, Marie-Christine, Joris, Virginie, Craps, Julie |
| المساهمون: | UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, Thyroid Research Group, Division of Infection & Immunity, Cardiff University School of Medicine - Heath Park, Cardiff CF14 4XN, UK, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique |
| المصدر: | International journal of molecular sciences, Vol. 22, no.8 (2021) |
| سنة النشر: | 2021 |
| المجموعة: | DIAL@USL-B (Université Saint-Louis, Bruxelles) |
| مصطلحات موضوعية: | Adult, Autoimmune Diseases, Autoimmunity, Biomarkers, Cytokines, Female, Fluorescent Antibody Technique, Gene Expression Regulation, Hashimoto Disease, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Immunohistochemistry, Male, Middle Aged, Models, Biological, NADPH Oxidase 2, Oxidative Stress, Reactive Oxygen Species, Sirtuin 1, Superoxide Dismutase-1, T-Lymphocyte Subsets, Th1 Cells, Thymocytes, Thyroid Function Tests, Thyroid Gland, Vascular Endothelial Growth Factor A, Young Adult, HIF-1α |
| الوصف: | In Hashimoto's thyroiditis (HT), oxidative stress (OS) is driven by Th1 cytokines' response interfering with the normal function of thyrocytes. OS results from an imbalance between an excessive production of reactive oxygen species (ROS) and a lowering of antioxidant production. Moreover, OS has been shown to inhibit Sirtuin 1 (SIRT1), which is able to prevent hypoxia-inducible factor (HIF)-1α stabilization. The aims of this study were to determine the involvement of NADPH-oxidases (NOX), SIRT1, and HIF-1α in HT pathophysiology as well as the status of antioxidant proteins such as peroxiredoxin 1 (PRDX1), catalase, and superoxide dismutase 1 (SOD1). The protein expressions of NOX2, NOX4, antioxidant enzymes, SIRT1, and HIF-1α, as well as glucose transporter-1 (GLUT-1) and vascular endothelial growth factor A (VEGF-A), were analyzed by Western blot in primary cultures of human thyrocytes that were or were not incubated with Th1 cytokines. The same proteins were also analyzed by immunohistochemistry in thyroid samples from control and HT patients. In human thyrocytes incubated with Th1 cytokines, NOX4 expression was increased whereas antioxidants, such as PRDX1, catalase, and SOD1, were reduced. Th1 cytokines also induced a significant decrease of SIRT1 protein expression associated with an upregulation of HIF-1α, GLUT-1, and VEGF-A proteins. With the exception of PRDX1 and SOD1, similar results were obtained in HT thyroids. OS due to an increase of ROS produced by NOX4 and a loss of antioxidant defenses (PRDX1, catalase, SOD1) correlates to a reduction of SIRT1 and an upregulation of HIF 1α, GLUT-1, and VEGF-A. Our study placed SIRT1 as a key regulator of OS and we, therefore, believe it could be considered as a potential therapeutic target in HT. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1422-0067 |
| العلاقة: | boreal:248138; http://hdl.handle.net/2078.1/248138Test; info:pmid/33916948; urn:EISSN:1422-0067 |
| DOI: | 10.3390/ijms22083806 |
| الإتاحة: | https://doi.org/10.3390/ijms22083806Test http://hdl.handle.net/2078.1/248138Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.5B3C55F7 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14220067 |
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| DOI: | 10.3390/ijms22083806 |