Evidence that an Iodolactone Mediates the Inhibitory Effect of Iodide on Thyroid Cell Proliferation but not on Adenosine 3′,5′-Monophosphate Formation

Dugrillon, A.; Bechtner, G.; Uedelhoven, Waltraud M.; Weber, P. C.; Gärtner, Roland

doi:10.1210/endo-127-1-337

Cited by 60 publications

(54 citation statements)

References 27 publications

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“…This inhibitory activity therefore seemed to be nondialysable and different from the previously reported autoantibodies as well as iodine or iodolactone, a mediator of the inhibitory effect of iodine [23,24].…”

Section: Discussioncontrasting

confidence: 87%

Thyroid Cell Proliferation-lnhibiting Activity in Serum of Patients with Chronic Renal Failure on Hemodialysis.

et al. 1996

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Section: Discussioncontrasting

confidence: 87%

Thyroid Cell Proliferation-lnhibiting Activity in Serum of Patients with Chronic Renal Failure on Hemodialysis.

et al. 1996

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“…␣-Iodohexadecanal (alpha-IHDA) is a major iodolipid that has multiple inhibitory effects on adenylate cyclase, NADPH-oxidase, and thyroid peroxidase (52)(53)(54). Another iodolipid, 6-iodo-5-hydroxy-8,11,14-eicosatrienoic acid ⌬-lactone (⌬-iodolactone) is known to specifically inhibit signal transduction pathways induced by local growth factors, such as epidermal growth factor and basic fibroblast growth factor (55). These iodocompounds seem to act as mediators of iodine function as an antioxidant and autoregulation of cAMPindependent thyroid cell proliferation, and the possibility of formation of such iodocompounds in iodine-treated breast cancer cells needs to be investigated as hypothesized earlier (56).…”

Section: Discussionmentioning

confidence: 99%

Molecular Iodine Induces Caspase-independent Apoptosis in Human Breast Carcinoma Cells Involving the Mitochondria-mediated Pathway

Shrivastava

Tiwari

Sinha

et al. 2006

Journal of Biological Chemistry

120

104

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Iodine-induced apoptosis was independent of caspases. Iodine dissipated mitochondrial membrane potential, exhibited antioxidant activity, and caused depletion in total cellular thiol content. Western blot results showed a decrease in Bcl-2 and up-regulation of Bax. Immunofluorescence studies confirmed the activation and mitochondrial membrane localization of Bax. Ectopic Bcl-2 overexpression did not rescue iodine-induced cell death. Iodine treatment induces the translocation of apoptosis-inducing factor from mitochondria to the nucleus, and treatment of N-acetyl-L-cysteine prior to iodine exposure restored basal thiol content, ROS levels, and completely inhibited nuclear translocation of apoptosis-inducing factor and subsequently cell death, indicating that thiol depletion may play an important role in iodineinduced cell death. These results demonstrate that iodine treatment activates a caspase-independent and mitochondria-mediated apoptotic pathway.

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“…For example, iodohexadecanal mimics the inhibition of TSH-induced cAMP production in dog thyroid cells (Panneels et al 1994). In contrast, the inhibition of porcine thyroid growth induced by delta-iodolactone is epidermal growth factor/inositide dependent but cAMP independent (Dugrillon et al 1990).…”

Section: Introductionmentioning

confidence: 99%

Biological activity of activating thyrotrophin receptor mutants: modulation by iodide

Al-Khafaji¹,

Wiltshire²,

Führer³

et al. 2005

Journal of Molecular Endocrinology

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Epidemiological studies have revealed a significantly higher incidence of toxic adenoma (TA) and toxic multi-nodular goitre (TMNG) in regions of iodine deficiency. Fifty to eighty percent of TA and TMNG are caused by activation of the cAMP pathway, mostly by mutations in the thyrotrophin receptor (TSHR).We aimed to investigate whether iodide could modulate the biological effects of activating TSHR mutations. We have applied an in vitro model of TA comprising FRTL-5 cells stably expressing activating TSHR. We have mimicked the in vivo situation by examining the effects of prolonged exposure to iodide on the proliferation and signal transduction etc. of these cells.We observed an iodide-induced 'inhibition of proliferation' which was significant from 10 mM in the presence of serum but from 1 mM in its absence. The inhibition of proliferation was significantly higher in the activating mutant expressing FRTL-5 compared with control Neo or wild-type TSHR, indicating that the effect was mediated via the cAMP cascade. The effect was neither due to hyper-tonicity nor was it the result of an increase in cell death either by apoptosis or necrosis. Prolonged exposure to iodide produces an increase in cells in the G2 and post-G2 phases, indicating that G2/M blockade contributes to the mechanism of inhibition.The mutant expressing FRTL-5 cells have increased proliferation when chronically exposed to TSH, and this is associated with a reduction in phosphorylated (p) CREB levels. This contrasts with the effect of iodide in which inhibition of proliferation is accompanied by an increase in pCREB.In conclusion, our studies indicate that the biological effects of activating TSHR mutations vary with the ambient iodide supply and could be masked in regions of high iodine intake.

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Evidence that an Iodolactone Mediates the Inhibitory Effect of Iodide on Thyroid Cell Proliferation but not on Adenosine 3′,5′-Monophosphate Formation

Cited by 60 publications

References 27 publications

Thyroid Cell Proliferation-lnhibiting Activity in Serum of Patients with Chronic Renal Failure on Hemodialysis.

Thyroid Cell Proliferation-lnhibiting Activity in Serum of Patients with Chronic Renal Failure on Hemodialysis.

Molecular Iodine Induces Caspase-independent Apoptosis in Human Breast Carcinoma Cells Involving the Mitochondria-mediated Pathway

Biological activity of activating thyrotrophin receptor mutants: modulation by iodide

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