H2O2 induces apoptosis of pig thyrocytes in culture

Riou, Catherine; Rémy, Christian; Rabilloud, Rachida; Rousset, Bernard; Fonlupt, Pierre

doi:10.1677/joe.0.1560315

Cited by 26 publications

(17 citation statements)

References 31 publications

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“…Only about 4 ± 5 percent of thyroid follicular cells respond, without any change even after a 7 day exposure of high doses of iodide or d-iodolactone. This rapid induction of apoptosis by iodide has already been shown in vivo (Bechtner et al, 1999;Burikhanov and Matsuzaki, 2000) as well as in vitro by H 2 O 2 (Riou et al, 1999;Riou et al, 1998), iodide (Feldkamp et al, 1999), TNF (Bretz et al, 1999) and EGF and TGF-b (Bechtner et al, 1999;Gärtner et al, 1997). The follicular cells in our three dimensional system are functional active, and proliferate only after stimulation with growth factors or after iodide depletion (Gärtner et al, 1985;Bechtner et al, 1996).…”

Section: Discussionsupporting

confidence: 69%

“…Especially in thyroid autoimmune diseases like Hashimotos thyroiditis (Kotani et al, 1995) and Graves disease (Hirmomatsu et al, 1999) apoptosis seems to be related to the FAS/FASL pathway (Mitsiades et al, 1998). In vitro TGF-b and EGF (Bechtner et al, 1999), high doses of iodide (Vitale et al, 2000) or H 2 O 2 (Riou et al, 1998;Riou et al, 1999) also induce apoptosis of thyroid follicular cells.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Influence of Iodide and Iodolactones on Thyroid Apoptosis

Langer

Burzler

Bechtner

et al. 2003

Exp Clin Endocrinol Diabetes

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Iodine induced thyroid involution is caused by apoptosis rather than necrosis. This effect of iodide on apoptosis of thyroid epithelial cells may be not a direct one but mediated by iodinated derivatives i.e. of polyunsaturated fatty acids, especially of iodolactones, which have previously shown to inhibit thyroid cell proliferation. We studied the influence on apoptosis of iodide (2 microM and 20 microM) and iodolactone (0.05 microM and 0.5 microM), with and without TSH (1 mU/ml), using a well characterized ex vivo- culture system of intact porcine thyroid follicles in three-dimensional culture. Apoptosis and necrosis was evaluated by electron-microscopy. Stimulation with 2 and 20 microM iodide rapidly induced a rate of apoptosis (4 - 6 %) comparable to about 40-fold lower doses of delta-iodolactone (0.05 microM and 0.5 microM). Addition of TSH (1 mU/ml) caused a slight but not significant further increase of the incidence of apoptotic cells. The rate of necrotic thyroid epithelial cells (1 - 2 %) was similar in all experiments. As delta-iodolactone in very low concentrations--comparable to iodide in higher concentrations--not only inhibits growth but also induces apoptosis, it has to be supposed that the effect of iodide is mediated by this iodinated compound. However, further experiments are necessary to confirm this hypothesis. In addition it could be demonstrated, that apoptosis is a very rapid and limited process in intact follicles. This also may explain, why iodine supplementation even in high doses does not lead to thyroid atrophy but only normalisation of thyroid size. These results confirm that apoptosis is an important regulated and limited mechanism in goiter involution.

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Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Influence of Iodide and Iodolactones on Thyroid Apoptosis

Langer

Burzler

Bechtner

et al. 2003

Exp Clin Endocrinol Diabetes

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“…Previous in vitro studies (15,16) indicate that excess H 2 O 2 also is able to induce apoptosis, or programmed cell death, in the thyroid. The H 2 O 2 -mediated cytotoxicity appears to be dose-dependent, requiring only low concentrations to result in thyroid cell apoptosis rather then necrosis.…”

Section: Introductionmentioning

confidence: 98%

Selenium has a protective role in caspase-3-dependent apoptosis induced by H2O2 in primary cultured pig thyrocytes

Demelash

Karlsson

Nilsson

et al. 2004

European Journal of Endocrinology

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Objective: Hydrogen peroxide (H 2 O 2 ), necessary for thyroid hormonogenesis, is produced at the apical surface of the thyroid follicular epithelium. Excess H 2 O 2 is potentially cytotoxic and may contribute to the development of hypothyroidism, e.g. in severe selenium deficiency. Yet it is unclear how H 2 O 2 contributes to thyroid cell death. Design and methods: H 2 O 2 -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

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“…However, in studying thyrocyte iodide uptake and organification, all the above works employed iodine radioisotopes ( 125 I and 131 I), 21,22 which could somewhat contribute to the effects observed. 47 A consequence of the longterm thyrocyte incubation (24 h) with millimolar H 2 O 2 concentrations is induction of apoptosis 28,48 by activation of caspase-3 49 and cell necrosis. 49 Maintaining the thyroid follicular structure seems to hold significance in inactivating H 2 O 2 and remains the function of thyroid antioxidant system.…”

Section: Discussionmentioning

confidence: 99%

Effect of oxidative stress on rat thyrocyte iodide metabolism

Nadolnik

Niatsetskaya

Lupachyk

2007

Cell Biochemistry & Function

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Thyroid cells fall into the type of cells functioning during continuous production of high H(2)O(2) concentrations. We studied the effect of H(2)O(2)-induced oxidative stress (0.1, 1.0 and 10.0 mM) on the activities of the key steps of iodide metabolism (uptake, oxidation and organification) in thyrocytes cultivated in an organ culture. After 60 min cultivation of cells in a medium containing H(2)O(2) at concentrations of 1.0 and 10.0 mM iodide (I(-)) uptake, thyroperoxidase (TPO) activity and I(-) organification were completely inhibited. No restoration of the parameters studied was observed within the subsequent 24 h of cultivation. The inhibitory effect of 0.1 mM H(2)O(2) was reversible. Activation of I(-) uptake in the cultivated tissue and a 520-880% increase of the total I(-) content were observed after 8 and 24 h. The concentration of I(-) protein-bound fraction was raised by 220% after 24 h. A biphasic effect of 0.1 mM H(2)O(2) on TPO was observed: 76.2% and 72.2% inhibitions were seen after 2 and 8 h, respectively, whereas 40.0% enzyme activation was after 5 h. TPO activity was partially restored after 24 h and amounted to 65% of the initial value. The significant increase in the concentration of iodide protein-bound fraction, which was observed simultaneously with TPO inhibition, could be due to thyroglobulin non-enzymic iodination under H(2)O(2)-generated oxidative stress. The data obtained indicate that iodide oxidation, as a step in the biosynthesis of thyroid hormones, was most sensitive to oxidative stress activation. The impaired iodide uptake and its organification during oxidative stress can play a pathogenetic role in disturbed functions of thyroid cells.

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H2O2 induces apoptosis of pig thyrocytes in culture

Cited by 26 publications

References 31 publications

Influence of Iodide and Iodolactones on Thyroid Apoptosis

Influence of Iodide and Iodolactones on Thyroid Apoptosis

Selenium has a protective role in caspase-3-dependent apoptosis induced by H2O2 in primary cultured pig thyrocytes

Effect of oxidative stress on rat thyrocyte iodide metabolism

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