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Mikael Nilsson - One of the best experts on this subject based on the ideXlab platform.
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EXPERIMENTAL STUDY Selenium has a protective role in caspase-3-dependent apoptosis induced by H2O2 in primary cultured pig thyrocytes
2015Co-Authors: Abeba Demelash, Jan-olof Karlsson, Mikael NilssonAbstract:Objective: Hydrogen peroxide (H2O2), necessary for Thyroid hormonogenesis, is produced at the apical surface of the Thyroid Follicular Epithelium. Excess H2O2 is potentially cytotoxic and may contribute to the development of hypoThyroidism, e.g. in severe selenium deficiency. Yet it is unclear how H2O2 con-tributes to Thyroid cell death. Design and methods: H2O2-induced apoptosis and necrosis were studied in primary cultured pig Thyroid cells. Glutathione peroxidase (GPx) activity was altered by culture in low serum with or without sele-nite substitution. Apoptosis was evaluated by spectrofluorometric measurement of caspase-3-specific substrate cleavage, and by analysis of DNA fragmentation by agarose gel electrophoresis. Necrosis was detected by 51Cr release from prelabeled cells. Results: Exogenous H2O2 dose-dependently (100–400mmol/l) activated caspase-3 within 3–12 h, and DNA degradation was observed after 24 h. The potency of H2O2 to induce apoptosis was low com-pared with that of staurosporine, a strong proapoptotic agent. H2O2-treated cells with reduced GPx activity showed increased caspase-3 activation. Incubation of serum-starved cells with selenite (10 –100 nmol/l) normalized the GPx activity and reduced the activation of caspase-3 by H2O2. High H2O2 concentrations (400–800mmol/l) were required to obtain necrosis. The H2O2-induced necrosis was exaggerated by both low GPx activity and catalase inhibition. Conclusions: Cytotoxic effects of H2O2 on Thyroid cells include caspase-3-dependent apoptosis that occurs at H2O2 concentrations insufficient to induce necrosis. Selenium deficiency aggravates the apoptotic response, probably due to impaired capacity of GPx to degrade H2O2. European Journal of Endocrinology 150 841–84
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Selenium has a protective role in caspase-3-dependent apoptosis induced by H2O2 in primary cultured pig thyrocytes
European Journal of Endocrinology, 2004Co-Authors: Abeba Demelash, Mikael Nilsson, Jan-olof Karlsson, U. BjörkmanAbstract:Objective: Hydrogen peroxide (H2O2), necessary for Thyroid hormonogenesis, is produced at the apical surface of the Thyroid Follicular Epithelium. Excess H2O2 is potentially cytotoxic and may contribute to the development of hypoThyroidism, e.g. in severe selenium deficiency. Yet it is unclear how H2O2 contributes to Thyroid cell death. Design and methods :H 2O2-induced apoptosis and necrosis were studied in primary cultured pig Thyroid cells. Glutathione peroxidase (GPx) activity was altered by culture in low serum with or without selenite substitution. Apoptosis was evaluated by spectrofluorometric measurement of caspase-3-specific substrate cleavage, and by analysis of DNA fragmentation by agarose gel electrophoresis. Necrosis was detected by 51 Cr release from prelabeled cells. Results: Exogenous H2O2 dose-dependently (100 – 400mmol/l) activated caspase-3 within 3 – 12 h, and DNA degradation was observed after 24 h. The potency of H2O2 to induce apoptosis was low compared with that of staurosporine, a strong proapoptotic agent. H2O2-treated cells with reduced GPx activity showed increased caspase-3 activation. Incubation of serum-starved cells with selenite (10 – 100 nmol/l) normalized the GPx activity and reduced the activation of caspase-3 by H2O2. High H2O2 concentrations (400 – 800mmol/l) were required to obtain necrosis. The H2O2-induced necrosis was exaggerated by both low GPx activity and catalase inhibition. Conclusions: Cytotoxic effects of H2O2 on Thyroid cells include caspase-3-dependent apoptosis that occurs at H2O2 concentrations insufficient to induce necrosis. Selenium deficiency aggravates the apoptotic response, probably due to impaired capacity of GPx to degrade H2O2.
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Structural and functional aspects of the Thyroid Follicular Epithelium.
Toxicology Letters, 1992Co-Authors: Lars E. Ericson, Mikael NilssonAbstract:Abstract The Thyroid Epithelium is morphologically and functionally polarized, with an apical surface facing the Follicular lumen containing colloid and a basolateral surface facing the interstitium. Iodination and Thyroid hormone synthesis occur in the colloid at the apical plasma membrane. The introduction by Mauchamp et al. of primary cultures of porcine Thyroid cells grown as a polarized, confluent monolayer on a filter in a bicameral chamber system has now made it possible to study in more detail the barrier function and vectorial ion transport in the Thyroid Epithelium. The Follicular cells form a very tight monolayer (transepithelial resistance > 6000 ohm cm2) and establish a transepithelial potential difference (apical medium negative) of about 20 mV. These parameters are rapidly influenced by TSH, mainly by an action on apical sodium channels, and by EGF. The integrity of the barrier is, as in other epithelia, dependent on extracellular calcium. A calcium-dependent cell adhesion molecule, uvomorulin, is expressed at the lateral plasma membrane surface. EGF induces cell proliferation as well as migration of some of the epithelial cells to a position below the monolayer, which however maintains its polarity and barrier function. In contrast, during TPA-induced proliferation the barrier function is disrupted. Iodide is vectorially transported in basoapical direction while the epithelial layer is virtually impermeable for iodide transfer in the opposite direction. Iodide is concentrated in the cell by the basolateral “iodide-pump” and its efflux across the apical plasma membrane is rapidly and selectively increased by TSH via cAMP. EGF inhibits vectorial basoapical iodide transport mainly by reducing the iodide permeability of the apical plasma membrane. Together, these recent observations indicate that the ion content of the Follicular lumen is strictly controlled by the Thyroid Epithelium.
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Integrity of the occluding barrier in high-resistant Thyroid Follicular Epithelium in culture. II. Immediate protective effect of TSH on paracellular leakage induced by Ca2+ removal and cytochalasin B.
European journal of cell biology, 1991Co-Authors: Mikael Nilsson, J. Mölne, Lars E. EricsonAbstract:The acute influence of thyrotropin (TSH) on the Ca2+ and cytoskeleton dependence of the Thyroid epithelial occluding barrier was investigated in porcine thyrocyte monolayers cultured on filter support. The barrier function was assayed by measurements of the transepithelial resistance (RTE) and the apicobasal flux (FTE) of radiotracers (125I-; [3H]inulin) as well as by morphological examination of junctions (fluorescein isothiocyanate-phalloidin labeling of F-actin; electron microscopy). Removal of extracellular Ca2+ (Ca2+e) by ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) rapidly decreased RTE and increased FTE of both radiotracers. These changes were inhibited by TSH (1 mU/ml) given 6 min before Ca2+e removal. The inhibitory effect was total when Ca2+e was removed from the basal medium and partial when the cultures were totally deprived of Ca2+e. TSH added 10 min after basal depletion of Ca2+e partially reversed the changes in RTE and FTE. TSH also potentiated the recovery of RTE and FTE seen after readdition of Ca2+e. In contrast to Ca2+e-depleted cultures, the distribution of F-actin at the level of the junctional complex as well as the junctional ultrastructure were normal in cultures stimulated with TSH before depletion. TSH was also found to abolish the paracellular leakage induced by cytochalasin B (50 microM). TSH per se did not influence FTE of radiotracers. The observed effects of TSH were in all respects reproduced by forskolin (50 microM). In conclusion, acute stimulation with TSH protects the barrier function of porcine thyrocyte monolayers from the otherwise deleterious influence of Ca2+e-chelating and microfilament-disruptive agents. This effect of TSH is mediated by cyclic AMP. The data indicate that the integrity of the Thyroid occluding barrier not only remains but is strengthened in TSH-stimulated cultures. The possible involvement of cell adhesion molecules in this response to TSH is discussed.
Masayori Furudate - One of the best experts on this subject based on the ideXlab platform.
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Autoradiographic analysis of [^14C]deoxy-D-glucose in Thyroid cancer xenografts: A comparative study with pathologic correlation
Annals of Nuclear Medicine, 1994Co-Authors: Masahiro Kubota, Takatoshi Tsuda, Takashi Minase, Kunihiro Nakada, Masayori FurudateAbstract:An experimental model of Thyroid cancer was prepared for evaluating the accumulation of [^14C]deoxy-D-glucose ([^14C]DG) in Thyroid cancer xenografts (AC2). A continuous cell line established from a biopsy specimen of a metastatic Thyroid carcinoma possessed the ability to synthesize the cellular protein without increase in cell division after adding bovine TSH in vitro . The histological sections of the xenografts resected from the^131I treated nude mice mainly consisted of structures showing Follicular and trabecular growth. Immunohistochemically the cytoplasm of the tumor cells was positive for human thyroglobulin(hTg). These observations provide strong evidence that the AC2 cell originates in the Thyroid Follicular Epithelium. By comparing autoradiographic accumulation patterns of [^14C]DG and histopathological examinations, it was found that the uptake of [^14C]DG was higher in the granulation tissues surrounding necrosis than in viable tumor cells of trabeculary growing and follicle forming tissues. It is suggested that the degree of [^14C]DG content reflects not only tumor cell viability and proliferation but also the inflammatory and degenerative reaction accompanying tumor cell growth.
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Autoradiographic analysis of [14C]deoxy-D-glucose in Thyroid cancer xenografts: a comparative study with pathologic correlation.
Annals of Nuclear Medicine, 1994Co-Authors: Masahiro Kubota, Takatoshi Tsuda, Takashi Minase, Kunihiro Nakada, Masayori FurudateAbstract:An experimental model of Thyroid cancer was prepared for evaluating the accumulation of [14C]deoxy-D-glucose ([14C]DG) in Thyroid cancer xenografts (AC2). A continuous cell line established from a biopsy specimen of a metastatic Thyroid carcinoma possessed the ability to synthesize the cellular protein without increase in cell division after adding bovine TSHin vitro. The histological sections of the xenografts resected from the131I treated nude mice mainly consisted of structures showing Follicular and trabecular growth. Immunohistochemically the cytoplasm of the tumor cells was positive for human thyroglobulin(hTg). These observations provide strong evidence that the AC2 cell originates in the Thyroid Follicular Epithelium. By comparing autoradiographic accumulation patterns of [14C]DG and histopathological examinations, it was found that the uptake of [14C]DG was higher in the granulation tissues surrounding necrosis than in viable tumor cells of trabeculary growing and follicle forming tissues.
Milošević Verica - One of the best experts on this subject based on the ideXlab platform.
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The phytoestrogen genistein prevents trabecular bone loss and affects Thyroid Follicular cells in a male rat model of osteoporosis.
2018Co-Authors: Filipović Branko, Šošić-jurjević Branka, Živanović Jasmina, Manojlović-stojanoski Milica, Nestorović Nataša, Trifunović Svetlana, Ajdžanović Vladimir, Ristić Nataša, Milošević VericaAbstract:As a major phytoestrogen of soy, genistein effectively prevents bone loss in both humans and rat models of osteoporosis. However, although the bone-sparing effects of genistein are achieved directly through estrogen receptors, its mode of action on bone by modulation of other endocrine functions is not entirely clear. Thus, Thyroid hormones and calcitonin (CT) have an essential influence on bone metabolism. Besides its action on bones, in this study we examined the effect of genistein on the activity of two different endocrine cell populations, Thyroid Follicular and C-cells. Fifteen-month-old Wistar rats were either bilaterally orchidectomized (Orx) or sham-operated (SO). Two weeks after surgery, half of the Orx rats were treated chronically with 30 mg kg-1 b.w. genistein (Orx + G) subcutaneously (s.c.) every day for 3 weeks, while the remaining Orx rats and the SO rats were given the same volume of sterile olive oil to serve as controls. For histomorphometrical analysis of the trabecular bone microarchitecture an ImageJ public domain image processing programme was used. Thyroid sections were analysed histologically and stereologically after visualization of Follicular and C-cells by immunohistochemical staining for thyroglobulin and CT. Thyroid Follicular Epithelium, interstitium, colloid and CT-immunopositive C-cells were examined morphometrically. Serum concentrations of osteocalcin (OC), triiodothyronine (T3 ), thyroxine (T4 ) and CT were determined as well as urinary calcium (Ca2+ ) concentrations. Genistein treatment significantly increased cancellous bone area (B.Ar), trabecular thickness (TbTh) and trabecular number (TbN) (P < 0.05), but trabecular separation (Tb.Sp) was decreased (P < 0.05) compared with control Orx rats. In the Thyroid, genistein treatment significantly elevated the relative volume density (Vv) of the Follicular cells (P < 0.05) compared with Orx, whereas Vv of the colloid was lower (P < 0.05) than in the Orx. Evaluation of the biochemical parameters showed significant reductions in serum OC, T3 , T4 and urinary Ca2+ concentrations (P < 0.05), compared with Orx rats. These data indicate that genistein treatment improves the trabecular microarchitecture of proximal tibia, induces histomorphometrical changes in Thyroid glands, and decreases circulating Thyroid hormone levels in orchidectomized rat model of male osteoporosis
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Salmon calcitonin affects Thyroid endocrine cells and trabecular bone in a rat model of male osteoporosis
BioScientifica, 2017Co-Authors: Filipović Branko, Šošić-jurjević Branka, Živanović Jasmina, Manojlović-stojanoski Milica, Nestorović Nataša, Trifunović Svetlana, Jarić Ivana, Ušćebrka Gordana, Milošević VericaAbstract:Calcitonin (CT) is a hypocalcemic hormone produced by Thyroid C-cells that acts as an bone antiresorptive agent. The other endocrine cell population in Thyroid, called Follicular cells produce Thyroid hormones (TH) which also affect bone turnover. In this study, we evaluated the effects of salmon CT administration on structure and function of both CT and TH producing Thyroid cells as well as trabecular bone microarchitecture in orchidectomized (Orx) middle-aged rats. Fifteen-month-old male Wistar rats were either Orx or sham-operated (SO). One group of Orx animals were injected subcutaneously with synthetic salmon CT (Orx + CT; 100 IU/kg b.w.) every second day for 6 weeks. The rats from SO and second Orx group received the same volume of vehicle alone by the same schedule. The peroxidase–antiperoxidase method was applied for localization of CT in C-cells. CT-immunopositive Thyroid C-cells, Thyroid Follicular Epithelium, interstitium and colloid were evaluated morphometrically. An ImageJ public domain image processing program was used to measure bone histomorphometric parameters of the proximal tibial specimens. Blood serum samples were analyzed for CT, osteocalcin (OC) and thyroxine (T4), and urine samples fot calcium (Ca2+) concentration. We found a significant decrease in the Vc and Vv of Thyroid C-cells after CT treatment compared to both SO and Orx. The Vv of the colloid was higher, while VV of the Follicular Epithelium was lower after CT treatment compared to Orx. Analysis of trabecular microarchitecture showed that salmon CT administration significantly increases of cancellous bone area (B.Ar), trabecular thickness (Tb.Th), and trabecular number (Tb.N) whereas trabecular separation (Tb.Sp) was significantly decreased. CT treatment markedly elevated serum CT, but serum OC, T4 and urinary Ca2+ concentrations were lower than in the Orx group. These findings indicate that administration of salmon CT inhibited calcitonin-producing Thyroid C-cells and changes the structure of the Thyroid gland indicating hypoactivity
Masahiro Kubota - One of the best experts on this subject based on the ideXlab platform.
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Autoradiographic analysis of [^14C]deoxy-D-glucose in Thyroid cancer xenografts: A comparative study with pathologic correlation
Annals of Nuclear Medicine, 1994Co-Authors: Masahiro Kubota, Takatoshi Tsuda, Takashi Minase, Kunihiro Nakada, Masayori FurudateAbstract:An experimental model of Thyroid cancer was prepared for evaluating the accumulation of [^14C]deoxy-D-glucose ([^14C]DG) in Thyroid cancer xenografts (AC2). A continuous cell line established from a biopsy specimen of a metastatic Thyroid carcinoma possessed the ability to synthesize the cellular protein without increase in cell division after adding bovine TSH in vitro . The histological sections of the xenografts resected from the^131I treated nude mice mainly consisted of structures showing Follicular and trabecular growth. Immunohistochemically the cytoplasm of the tumor cells was positive for human thyroglobulin(hTg). These observations provide strong evidence that the AC2 cell originates in the Thyroid Follicular Epithelium. By comparing autoradiographic accumulation patterns of [^14C]DG and histopathological examinations, it was found that the uptake of [^14C]DG was higher in the granulation tissues surrounding necrosis than in viable tumor cells of trabeculary growing and follicle forming tissues. It is suggested that the degree of [^14C]DG content reflects not only tumor cell viability and proliferation but also the inflammatory and degenerative reaction accompanying tumor cell growth.
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Autoradiographic analysis of [14C]deoxy-D-glucose in Thyroid cancer xenografts: a comparative study with pathologic correlation.
Annals of Nuclear Medicine, 1994Co-Authors: Masahiro Kubota, Takatoshi Tsuda, Takashi Minase, Kunihiro Nakada, Masayori FurudateAbstract:An experimental model of Thyroid cancer was prepared for evaluating the accumulation of [14C]deoxy-D-glucose ([14C]DG) in Thyroid cancer xenografts (AC2). A continuous cell line established from a biopsy specimen of a metastatic Thyroid carcinoma possessed the ability to synthesize the cellular protein without increase in cell division after adding bovine TSHin vitro. The histological sections of the xenografts resected from the131I treated nude mice mainly consisted of structures showing Follicular and trabecular growth. Immunohistochemically the cytoplasm of the tumor cells was positive for human thyroglobulin(hTg). These observations provide strong evidence that the AC2 cell originates in the Thyroid Follicular Epithelium. By comparing autoradiographic accumulation patterns of [14C]DG and histopathological examinations, it was found that the uptake of [14C]DG was higher in the granulation tissues surrounding necrosis than in viable tumor cells of trabeculary growing and follicle forming tissues.
D. Wynford-thomas - One of the best experts on this subject based on the ideXlab platform.
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Thyroid epithelial cell transformation by a retroviral vector expressing SV40 large
2013Co-Authors: J. S. Burns, L. Lemoine, N. R. Lemoine, Dillwyn E. Williams, D. Wynford-thomasAbstract:Summary A recombinant murine retroviral vector encoding the SV40 virus large T antigen was used to infect stably an immortal line of differentiated rat Thyroid epithelial cells, FRTL-5. Expression of SV40 T transformed these cells to anchorage independence and tumorigenicity but did not alter morphology or abolish tissue-specific functions and growth factor requirements. The resulting phenotype provides a model of well-differentiated human Thyroid cancer. Despite the comparative rarity of Thyroid cancer, there are many advantages in using the Thyroid as a model for the study of multi-stage carcinogenesis in human and rodent epithelial cells. In contrast, for example, to that of gut and breast, the Thyroid Follicular Epithelium can be regarded from a differentiation and cell kinetic standpoint as a single homogeneous population whose growth is regulated in vivo by a single major growth factor- Thyroid stimulating hormone, TSH (Dumont, 1971). A spectrum of benign and malignant epithelial tumours occurs spontaneously in ma
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Immunocytochemically detectable TGF-beta associated with malignancy in Thyroid epithelial neoplasia.
Growth factors (Chur Switzerland), 1990Co-Authors: B Jasani, N. R. Lemoine, F S Wyllie, P A Wright, E D Williams, D. Wynford-thomasAbstract:The possible role of changes in TGF-beta expression in the multistage development of Thyroid cancer was assessed. The presence of TGF-beta 1 in Thyroid epithelial cells was analyzed in sections of normal and tumor tissue using an immunoperoxidase technique employing an antibody directed against the amino-terminal 30 amino acids of mature TGF-beta 1. Specific immunostaining was clearly detected in epithelial cells in 58% of malignant Thyroid tumours (including Follicular, papillary, and anaplastic variants). However, no positive cells were seen in any of 7 benign tumors nor in any normal Thyroid Epithelium. Within the cancer group as a whole, there was no significant correlation with pathological grade or clinical stage of tumor but in one subgroup--Follicular carcinomas--a significant association was noted between TGF-beta immunostaining and the presence of a specific mutation of the H-ras oncogene (codon 61, gln----arg). We conclude that a major alteration in expression of TGF-beta occurs specifically in the malignant stage of tumor development in Thyroid Follicular Epithelium and speculate on its possible role in this process.