scholarly journals Sexual Dimorphism of NADPH Oxidase/H2O2 System in Rat Thyroid Cells; Effect of Exogenous 17β-Estradiol

2018 ◽  
Vol 19 (12) ◽  
pp. 4063 ◽  
Author(s):  
Jan Stepniak ◽  
Andrzej Lewinski ◽  
Malgorzata Karbownik-Lewinska
Keyword(s):  
Sexual Dimorphism ◽  
Nadph Oxidase ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Thyroid Diseases ◽  
Female Rats ◽  
H2o2 Production ◽  
Thyroid Cells ◽  
Dual Oxidase ◽  
17Β Estradiol ◽  
Rat Thyroid

It has long been observed that females are more susceptible to thyroid diseases than males. Epidemiological and experimental data show that actions of hormonal factors—especially estrogens—may explain such disparity. However, the exact cause and mechanisms of this sexual dimorphism remain so far unknown. Therefore, we aimed at evaluating the effect of 17β-estradiol on the redox balance in thyroids of male and female rats. Expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, i.e., dual oxidase 1 (DUOX1), dual oxidase 2 (DUOX2) and NADPH oxidase 4 (NOX4), and hydrogen peroxide (H2O2) levels were evaluated in the primary cell cultures derived from thyroid glands of adult male or female Wistar rats. The measurement was made before and after treatment with 17β-estradiol alone or with addition of one of its receptor antagonists. We found that under basal conditions female thyroid cells are exposed to higher concentrations of H2O2, most likely due to NOX/DUOX enzymes activity. Additionally, exogenous 17β-estradiol stimulated NOX/DUOX expression as well as H2O2 production, and this effect was mainly mediated through ERα. In conclusion, oxidative processes may constitute mechanisms responsible for sexual dimorphism of thyroid diseases. Exogenous 17β-estradiol may play a crucial pathogenic role in thyroid diseases via oxidative mechanisms, however without any gender differences.

Dual oxidase, hydrogen peroxide and thyroid diseases

2010 ◽  
Vol 235 (4) ◽  
pp. 424-433 ◽  
Author(s):  
Hidemi Ohye ◽  
Masahiro Sugawara
Keyword(s):  
Hydrogen Peroxide ◽  
Thyroid Gland ◽  
Nadph Oxidase ◽  
Thyroid Diseases ◽  
Human Thyroid ◽  
Apical Plasma Membrane ◽  
Thyroid Cell ◽  
Thyroid Cells ◽  
Nadph Oxidase 4 ◽  
Dual Oxidase

The thyroid gland is a unique endocrine organ that requires hydrogen peroxide (H2O2) for thyroid hormone formation. The molecule for H2O2 production in the thyroid gland has been known as dual oxidase 2 (DUOX2). Recently, NADPH oxidase 4 (NOX4), a homolog of the NOX family, was added as a new intracellular source of reactive oxygen species (ROS) in the human thyroid gland. This review focuses on the recent progress of the DUOX system and its possible contribution to human thyroid diseases. Also, we discuss human thyroid diseases related to abnormal H2O2 generation. The DUOX molecule contains peroxidase-like and NADPH oxidase-like domains. Human thyroid gland also contains DUOX1 that shares 83% similarity with the DUOX2 gene. However, thyroid DUOX1 protein appears to play a minor role in H2O2 production. DUOX proteins require DUOX maturation or activation factors (DUOXA1 or 2) for proper translocation of DUOX from the endoplasmic reticulum to the apical plasma membrane, where H2O2 production takes place. Thyroid cells contain antioxidants to protect cells from the H2O2-mediated oxidative damage. Loss of this balance may result in thyroid cell dysfunction and thyroid diseases. Mutation of either DUOX2 or DUOXA2 gene is a newly recognized cause of hypothyroidism due to insufficient H2O2 production. Papillary thyroid carcinoma, the most common thyroid cancer, is closely linked to the increased ROS production by NOX4. Hashimoto's thyroiditis, a common autoimmune thyroid disease in women, becomes conspicuous when iodide intake increases. This phenomenon may be explained by the abnormality of iodide-induced H2O2 or other ROS in susceptible individuals. Discovery of DUOX proteins and NOX4 provides us with valuable tools for a better understanding of pathophysiology of prevalent thyroid diseases.

Transient congenital hypothyroidism caused by compound heterozygous mutations affecting the NADPH-oxidase domain of DUOX2

2016 ◽  
Vol 29 (3) ◽  
Author(s):  
Atsuko Yoshizawa-Ogasawara ◽  
Kiyomi Abe ◽  
Sayaka Ogikubo ◽  
Satoshi Narumi ◽  
Tomonobu Hasegawa ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Congenital Hypothyroidism ◽  
Nicotinamide Adenine Dinucleotide ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Nicotinamide Adenine ◽  
Compound Heterozygous ◽  
Loss Of Function ◽  
Dual Oxidase ◽  
Compound Heterozygous Mutations ◽  
Transient Congenital Hypothyroidism

AbstractHere, we describe three cases of loss-of-function mutations in the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase (NOX) domain of dual oxidase 2 (

scholarly journals H2O2 Metabolism in Normal Thyroid Cells and in Thyroid Tumorigenesis: Focus on NADPH Oxidases

Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 126 ◽  
Author(s):  
Ildiko Szanto ◽  
Marc Pusztaszeri ◽  
Maria Mavromati
Keyword(s):  
Redox Regulation ◽  
Current Knowledge ◽  
H2o2 Production ◽  
Thyroid Cells ◽  
Hormone Synthesis ◽  
Physiological Processes ◽  
Pathological Conditions ◽  
The Family ◽  
Dual Oxidase ◽  
Nox Family

Thyroid hormone synthesis requires adequate hydrogen peroxide (H2O2) production that is utilized as an oxidative agent during the synthesis of thyroxin (T4) and triiodothyronine (T3). Thyroid H2O2 is generated by a member of the family of NADPH oxidase enzymes (NOX-es), termed dual oxidase 2 (DUOX2). NOX/DUOX enzymes produce reactive oxygen species (ROS) as their unique enzymatic activity in a timely and spatially regulated manner and therefore, are important regulators of diverse physiological processes. By contrast, dysfunctional NOX/DUOX-derived ROS production is associated with pathological conditions. Inappropriate DUOX2-generated H2O2 production results in thyroid hypofunction in rodent models. Recent studies also indicate that ROS improperly released by NOX4, another member of the NOX family, are involved in thyroid carcinogenesis. This review focuses on the current knowledge concerning the redox regulation of thyroid hormonogenesis and cancer development with a specific emphasis on the NOX and DUOX enzymes in these processes.

scholarly journals Sexual dimorphism and thyroid dysfunction: a matter of oxidative stress?

2014 ◽  
Vol 221 (2) ◽  
pp. R31-R40 ◽  
Author(s):  
Rodrigo S Fortunato ◽  
Andrea C F Ferreira ◽  
Fabio Hecht ◽  
Corinne Dupuy ◽  
Denise P Carvalho
Keyword(s):  
Oxidative Stress ◽  
Cell Proliferation ◽  
Sexual Dimorphism ◽  
Thyroid Dysfunction ◽  
Antioxidant Defense ◽  
Redox Balance ◽  
Female Rats ◽  
Male Rats ◽  
17Β Estradiol ◽  
Thyroid Dysfunctions

Thyroid diseases, such as autoimmune disease and benign and malignant nodules, are more prevalent in women than in men, but the mechanisms involved in this sex difference is still poorly defined. H2O2is produced at high levels in the thyroid gland and regulates parameters such as cell proliferation, migration, survival, and death; an imbalance in the cellular oxidant–antioxidant system in the thyroid may contribute to the greater incidence of thyroid disease among women. Recently, we demonstrated the existence of a sexual dimorphism in the thyrocyte redox balance, characterized by higher H2O2production, due to higher NOX4 and Poldip2 expression, and weakened enzymatic antioxidant defense in the thyroid of adult female rats compared with male rats. In addition, 17β-estradiol administration increasedNOX4mRNA expression and H2O2production in thyroid PCCL3 cells. In this review, we discuss the possible involvement of oxidative stress in estrogen-related thyroid pathophysiology. Our current hypothesis suggests that a redox imbalance elicited by estrogen could be involved in the sex differences found in the prevalence of thyroid dysfunctions.

scholarly journals Sex-dependent dysregulation of human neutrophil responses by bisphenol A

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Wioletta Ratajczak-Wrona ◽  
Marzena Garley ◽  
Malgorzata Rusak ◽  
Karolina Nowak ◽  
Jan Czerniecki ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Bisphenol A ◽  
Total Concentration ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Human Neutrophils ◽  
Boyden Chamber ◽  
No Production ◽  
Pathogen Elimination ◽  
Latex Beads

Abstract Background In the present study, we aimed to investigate selected functions of human neutrophils exposed to bisphenol A (BPA) under in vitro conditions. As BPA is classified among xenoestrogens, we compared its action and effects with those of 17β-estradiol (E2). Methods Chemotaxis of neutrophils was examined using the Boyden chamber. Their phagocytosis and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase activity were assessed via Park’s method with latex beads and Park’s test with nitroblue tetrazolium. To assess the total concentration of nitric oxide (NO), the Griess reaction was utilized. Flow cytometry was used to assess the expression of cluster of differentiation (CD) antigens. The formation of neutrophil extracellular traps (NETs) was analyzed using a microscope (IN Cell Analyzer 2200 system). Expression of the investigated proteins was determined using Western blot. Results The analysis of results obtained for both sexes demonstrated that after exposure to BPA, the chemotactic capacity of neutrophils was reduced. In the presence of BPA, the phagocytic activity was found to be elevated in the cells obtained from women and reduced in the cells from men. Following exposure to BPA, the percentage of neutrophils with CD14 and CD284 (TLR4) expression, as well as the percentage of cells forming NETs, was increased in the cells from both sexes. The stimulatory role of BPA and E2 in the activation of NADPH oxidase was observed only in female cells. On the other hand, no influence of E2 on the expression of CD14 and CD284, chemotaxis, phagocytosis, and the amount of NET-positive neutrophils was found for both sexes. The study further showed that BPA intensified NO production and iNOS expression in the cells of both sexes. In addition, intensified expression of all tested PI3K-Akt pathway proteins was observed in male neutrophils. Conclusions The study demonstrated the influence of BPA on neutrophil functions associated with locomotion and pathogen elimination, which in turn may disturb the immune response of these cells in both women and men. Analysis of the obtained data showed that the effect of this xenoestrogen on the human neutrophils was more pronounced than E2.

scholarly journals Characteristics of a lysosomal membrane transport system for tyrosine and other neutral amino acids in rat thyroid cells.

1986 ◽  
Vol 261 (36) ◽  
pp. 17107-17112
Author(s):  
J Bernar ◽  
F Tietze ◽  
L D Kohn ◽  
I Bernardini ◽  
G S Harper ◽  
...  
Keyword(s):  
Amino Acids ◽  
Membrane Transport ◽  
Transport System ◽  
Lysosomal Membrane ◽  
Thyroid Cells ◽  
Neutral Amino Acids ◽  
Rat Thyroid

scholarly journals Trace Amine-Associated Receptor 1 Trafficking to Cilia of Thyroid Epithelial Cells

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1518
Author(s):  
Maria Qatato ◽  
Vaishnavi Venugopalan ◽  
Alaa Al-Hashimi ◽  
Maren Rehders ◽  
Aaron D. Valentine ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cell Lines ◽  
Human Thyroid ◽  
Apical Plasma Membrane ◽  
Thyroid Cell ◽  
Thyroid Cells ◽  
Trace Amine ◽  
Rat Thyroid

Trace amine-associated receptor 1 (rodent Taar1/human TAAR1) is a G protein-coupled receptor that is mainly recognized for its functions in neuromodulation. Previous in vitro studies suggested that Taar1 may signal from intracellular compartments. However, we have shown Taar1 to localize apically and on ciliary extensions in rodent thyrocytes, suggesting that at least in the thyroid, Taar1 may signal from the cilia at the apical plasma membrane domain of thyrocytes in situ, where it is exposed to the content of the follicle lumen containing putative Taar1 ligands. This study was designed to explore mouse Taar1 (mTaar1) trafficking, heterologously expressed in human and rat thyroid cell lines in order to establish an in vitro system in which Taar1 signaling from the cell surface can be studied in future. The results showed that chimeric mTaar1-EGFP traffics to the apical cell surface and localizes particularly to spherical structures of polarized thyroid cells, procilia, and primary cilia upon serum-starvation. Moreover, mTaar1-EGFP appears to form high molecular mass forms, possibly homodimers and tetramers, in stably expressing human thyroid cell lines. However, only monomeric mTaar1-EGFP was cell surface biotinylated in polarized human thyrocytes. In polarized rat thyrocytes, mTaar1-EGFP is retained in the endoplasmic reticulum, while cilia were reached by mTaar1-EGFP transiently co-expressed in combination with an HA-tagged construct of the related mTaar5. We conclude that Taar1 trafficking to cilia depends on their integrity. The results further suggest that an in vitro cell model was established that recapitulates Taar1 trafficking in thyrocytes in situ, in principle, and will enable studying Taar1 signaling in future, thus extending our general understanding of its potential significance for thyroid autoregulation.

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