Oxidative Stress-Induced Sirtuin1 Downregulation Correlates to HIF-1α, GLUT-1, and VEGF-A Upregulation in Th1 Autoimmune Hashimoto’s Thyroiditis
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 bee...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-04-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/8/3806 |
| _version_ | 1797538591649300480 |
|---|---|
| author | Michaël Hepp Alexis Werion Axel De Greef Christine de Ville de Goyet Marc de Bournonville Catherine Behets Benoit Lengelé Chantal Daumerie Michel Mourad Marian Ludgate Marie-Christine Many Virginie Joris Julie Craps |
| author_facet | Michaël Hepp Alexis Werion Axel De Greef Christine de Ville de Goyet Marc de Bournonville Catherine Behets Benoit Lengelé Chantal Daumerie Michel Mourad Marian Ludgate Marie-Christine Many Virginie Joris Julie Craps |
| author_sort | Michaël Hepp |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T12:33:36Z |
| format | Article |
| id | doaj.art-25a70e323a7642bdaf66e3f1be09020d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:33:36Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-25a70e323a7642bdaf66e3f1be09020d2023-11-21T14:28:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01228380610.3390/ijms22083806Oxidative Stress-Induced Sirtuin1 Downregulation Correlates to HIF-1α, GLUT-1, and VEGF-A Upregulation in Th1 Autoimmune Hashimoto’s ThyroiditisMichaël Hepp0Alexis Werion1Axel De Greef2Christine de Ville de Goyet3Marc de Bournonville4Catherine Behets5Benoit Lengelé6Chantal Daumerie7Michel Mourad8Marian Ludgate9Marie-Christine Many10Virginie Joris11Julie Craps12Pole of Morphology, Faculty of Medicine, Institute of Experimental and Clinical Research, Université Catholique de Louvain, B-1200 Brussels, BelgiumPole of Morphology, Faculty of Medicine, Institute of Experimental and Clinical Research, Université Catholique de Louvain, B-1200 Brussels, BelgiumPole of Morphology, Faculty of Medicine, Institute of Experimental and Clinical Research, Université Catholique de Louvain, B-1200 Brussels, BelgiumPole of Morphology, Faculty of Medicine, Institute of Experimental and Clinical Research, Université Catholique de Louvain, B-1200 Brussels, BelgiumPole of Morphology, Faculty of Medicine, Institute of Experimental and Clinical Research, Université Catholique de Louvain, B-1200 Brussels, BelgiumPole of Morphology, Faculty of Medicine, Institute of Experimental and Clinical Research, Université Catholique de Louvain, B-1200 Brussels, BelgiumPole of Morphology, Faculty of Medicine, Institute of Experimental and Clinical Research, Université Catholique de Louvain, B-1200 Brussels, BelgiumEndocrinology Department, Faculty of Medicine, Université Catholique de Louvain, B-1200 Brussels, BelgiumSurgery and Abdominal Transplantation-Utragendo Department, Faculty of Medicine, Université Catholique de Louvain, B-1200 Brussels, BelgiumThyroid Research Group, Division of Infection & Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UKPole of Morphology, Faculty of Medicine, Institute of Experimental and Clinical Research, Université Catholique de Louvain, B-1200 Brussels, BelgiumPole of Pharmacology and Therapeutics, Faculty of Medicine, Institute of Experimental and Clinical Research, Université Catholique de Louvain, B-1200 Brussels, BelgiumPole of Morphology, Faculty of Medicine, Institute of Experimental and Clinical Research, Université Catholique de Louvain, B-1200 Brussels, BelgiumIn 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.https://www.mdpi.com/1422-0067/22/8/3806Hashimoto’s thyroiditisoxidative stressNOX4Sirtuin1HIF-1α |
| spellingShingle | Michaël Hepp Alexis Werion Axel De Greef Christine de Ville de Goyet Marc de Bournonville Catherine Behets Benoit Lengelé Chantal Daumerie Michel Mourad Marian Ludgate Marie-Christine Many Virginie Joris Julie Craps Oxidative Stress-Induced Sirtuin1 Downregulation Correlates to HIF-1α, GLUT-1, and VEGF-A Upregulation in Th1 Autoimmune Hashimoto’s Thyroiditis International Journal of Molecular Sciences Hashimoto’s thyroiditis oxidative stress NOX4 Sirtuin1 HIF-1α |
| title | Oxidative Stress-Induced Sirtuin1 Downregulation Correlates to HIF-1α, GLUT-1, and VEGF-A Upregulation in Th1 Autoimmune Hashimoto’s Thyroiditis |
| title_full | Oxidative Stress-Induced Sirtuin1 Downregulation Correlates to HIF-1α, GLUT-1, and VEGF-A Upregulation in Th1 Autoimmune Hashimoto’s Thyroiditis |
| title_fullStr | Oxidative Stress-Induced Sirtuin1 Downregulation Correlates to HIF-1α, GLUT-1, and VEGF-A Upregulation in Th1 Autoimmune Hashimoto’s Thyroiditis |
| title_full_unstemmed | Oxidative Stress-Induced Sirtuin1 Downregulation Correlates to HIF-1α, GLUT-1, and VEGF-A Upregulation in Th1 Autoimmune Hashimoto’s Thyroiditis |
| title_short | Oxidative Stress-Induced Sirtuin1 Downregulation Correlates to HIF-1α, GLUT-1, and VEGF-A Upregulation in Th1 Autoimmune Hashimoto’s Thyroiditis |
| title_sort | oxidative stress induced sirtuin1 downregulation correlates to hif 1α glut 1 and vegf a upregulation in th1 autoimmune hashimoto s thyroiditis |
| topic | Hashimoto’s thyroiditis oxidative stress NOX4 Sirtuin1 HIF-1α |
| url | https://www.mdpi.com/1422-0067/22/8/3806 |
| work_keys_str_mv | AT michaelhepp oxidativestressinducedsirtuin1downregulationcorrelatestohif1aglut1andvegfaupregulationinth1autoimmunehashimotosthyroiditis AT alexiswerion oxidativestressinducedsirtuin1downregulationcorrelatestohif1aglut1andvegfaupregulationinth1autoimmunehashimotosthyroiditis AT axeldegreef oxidativestressinducedsirtuin1downregulationcorrelatestohif1aglut1andvegfaupregulationinth1autoimmunehashimotosthyroiditis AT christinedevilledegoyet oxidativestressinducedsirtuin1downregulationcorrelatestohif1aglut1andvegfaupregulationinth1autoimmunehashimotosthyroiditis AT marcdebournonville oxidativestressinducedsirtuin1downregulationcorrelatestohif1aglut1andvegfaupregulationinth1autoimmunehashimotosthyroiditis AT catherinebehets oxidativestressinducedsirtuin1downregulationcorrelatestohif1aglut1andvegfaupregulationinth1autoimmunehashimotosthyroiditis AT benoitlengele oxidativestressinducedsirtuin1downregulationcorrelatestohif1aglut1andvegfaupregulationinth1autoimmunehashimotosthyroiditis AT chantaldaumerie oxidativestressinducedsirtuin1downregulationcorrelatestohif1aglut1andvegfaupregulationinth1autoimmunehashimotosthyroiditis AT michelmourad oxidativestressinducedsirtuin1downregulationcorrelatestohif1aglut1andvegfaupregulationinth1autoimmunehashimotosthyroiditis AT marianludgate oxidativestressinducedsirtuin1downregulationcorrelatestohif1aglut1andvegfaupregulationinth1autoimmunehashimotosthyroiditis AT mariechristinemany oxidativestressinducedsirtuin1downregulationcorrelatestohif1aglut1andvegfaupregulationinth1autoimmunehashimotosthyroiditis AT virginiejoris oxidativestressinducedsirtuin1downregulationcorrelatestohif1aglut1andvegfaupregulationinth1autoimmunehashimotosthyroiditis AT juliecraps oxidativestressinducedsirtuin1downregulationcorrelatestohif1aglut1andvegfaupregulationinth1autoimmunehashimotosthyroiditis |