Emerging roles of Keap1/Nrf2 signaling in the thyroid gland and perspectives for bench-to-bedside translation

Chartoumpekis, Dionysios V.; Ziros, Panos G.; Habeos, Ioannis; Sykiotis, Gerasimos P.

doi:10.1016/j.freeradbiomed.2022.08.021

Cited by 10 publications

(11 citation statements)

References 66 publications

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“…Areas with lower-selenium soil have been linked to increased Hashimoto thyroiditis in humans ( 104 ). Also, genetic interactions between minor alleles in the selenoprotein S gene ( SELENOS ) and the nuclear factor erythroid 2-related factor 2 gene ( NFE2L2 ) increase chronic thyroiditis incidences ( 105 ).…”

Section: Thyroid Diseases and Oxsmentioning

confidence: 99%

“…As the markers of OxS show a positive correlation with TSAb, it may indicate that these variables may be involved in the breakdown of redox balance ( 110 ). In patients with GD, activating the nuclear factor erythroid 2–related factor 2 (Nrf2) pathway may help restore thyroid function ( 105 ).…”

Section: Thyroid Diseases and Oxsmentioning

confidence: 99%

“…In PTC and anaplastic thyroid carcinoma, somatic KEAP1 and NFE2L2 mutations activating the Nrf2 pathway were discovered ( 128 , 129 ). Although the significance of such pathway activation in thyroid tumours is still unclear, it may help cancer cells survive ( 105 , 130 ). In addition, tumour tissue exhibit a higher quantity of ROS, which was linked to the decreased expression of selenium antioxidant proteins in cancer cells compared to healthy cells ( 122 ).…”

Section: Thyroid Diseases and Oxsmentioning

confidence: 99%

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The protective role of nutritional antioxidants against oxidative stress in thyroid disorders

et al. 2023

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An imbalance between pro-oxidative and antioxidative cellular mechanisms is oxidative stress (OxS) which may be systemic or organ-specific. Although OxS is a consequence of normal body and organ physiology, severely impaired oxidative homeostasis results in DNA hydroxylation, protein denaturation, lipid peroxidation, and apoptosis, ultimately compromising cells’ function and viability. The thyroid gland is an organ that exhibits both oxidative and antioxidative processes. In terms of OxS severity, the thyroid gland’s response could be physiological (i.e. hormone production and secretion) or pathological (i.e. development of diseases, such as goitre, thyroid cancer, or thyroiditis). Protective nutritional antioxidants may benefit defensive antioxidative systems in resolving pro-oxidative dominance and redox imbalance, preventing or delaying chronic thyroid diseases. This review provides information on nutritional antioxidants and their protective roles against impaired redox homeostasis in various thyroid pathologies. We also review novel findings related to the connection between the thyroid gland and gut microbiome and analyze the effects of probiotics with antioxidant properties on thyroid diseases.

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Section: Thyroid Diseases and Oxsmentioning

confidence: 99%

Section: Thyroid Diseases and Oxsmentioning

confidence: 99%

Section: Thyroid Diseases and Oxsmentioning

confidence: 99%

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The protective role of nutritional antioxidants against oxidative stress in thyroid disorders

et al. 2023

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“…The transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) has recently been recognized as the master regulator of the thyroid cell antioxidant response [8][9][10][11][12]. It controls the basal and inducible expression of a series of target genes that ensure a quick cellular response to oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Antioxidant Defense Capacity Is Reduced in Thyroid Stem/Precursor Cells Compared to Differentiated Thyrocytes

Gianì

Allia

Trovato

et al. 2023

IJMS

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There is much evidence linking oxidative stress to thyroid cancer, and stem cells are thought to play a key role in the tumor-initiating mechanism. Their vulnerability to oxidative stress is unexplored. This study aimed to comparatively evaluate the antioxidant capacity of stem/precursor thyroid cells and mature thyrocytes. Human stem/precursor cells and mature thyrocytes were exposed to increasing concentrations of menadione, an oxidative-stress-producing agent, and reactive oxygen species (ROS) production and cell viability were measured. The expression of antioxidant and detoxification genes was measured via qPCR as well as the total antioxidant capacity and the content of glutathione. Menadione elevated ROS generation in stem/precursor thyroid cells more than in mature thyrocytes. The ROS increase was inversely correlated (p = 0.005) with cell viability, an effect that was partially prevented by the antioxidant curcumin. Most thyroid antioxidant defense genes, notably those encoding for the glutathione-generating system and phase I detoxification enzymes, were significantly less expressed in stem/precursor thyroid cells. As a result, the glutathione level and the total antioxidant capacity in stem/precursor thyroid cells were significantly decreased. This reduced antioxidant defense may have clinical implications, making stem/precursor thyroid cells critical targets for environmental conditions that are not detrimental for differentiated thyrocytes.

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“…Thus, Kopàz et al [12] report that NRF2 deficiency leads to impairment of the gastrointestinal system in young females in connection with ERβ signaling. Current knowledge about the participation of NRF2 in physiology, pathophysiology and disease of the thyroid gland is analyzed by Chartoumpekis et al [13]. A comprehensive review of the role of NRF2 in protection against non-alcoholic steatohepatitis and its potential use as a pharmacological target is provided in Batish et al [14].…”

mentioning

confidence: 99%

Introduction to Special Issue on “Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases”

Cuadrado

Dinkova‐Kostova

Mann

2023

Free Radical Biology and Medicine

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Emerging roles of Keap1/Nrf2 signaling in the thyroid gland and perspectives for bench-to-bedside translation

Cited by 10 publications

References 66 publications

The protective role of nutritional antioxidants against oxidative stress in thyroid disorders

The protective role of nutritional antioxidants against oxidative stress in thyroid disorders

Antioxidant Defense Capacity Is Reduced in Thyroid Stem/Precursor Cells Compared to Differentiated Thyrocytes

Introduction to Special Issue on “Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases”

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