Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Differential gene expression analysis of iodide treated rat thyroid follicular cell line PCCl3

ABSTRACT: The inhibitory effect of supra physiological iodide concentrations on thyroid hormone synthesis (Wolff-Chaikoff effect) and thyrocyte proliferation is largely know as iodine autoregulation. However, the molecular mechanisms by which iodide excess modulate thyroid functions remains unclear. In this work, we analyzed the rat follicular cell PCCl3 transcriptome profile under untreated and treated conditions with 10-3M sodium iodide (Na/I). Serial Analysis of Gene Expression revealed several transcripts differentially expressed in response to the iodide showing that excess iodide affects almost all aspects of thyroid cell function and differentiation acting on the iodine autoregulatory mechanism through a complex process. Keywords: comparative genomic analysis PCCl3 cells were cultured under untreated and treated conditions with 10-3M NaI during 24 hours

ORGANISM(S): Rattus norvegicus

SUBMITTER: Edna Kimura

PROVIDER: E-GEOD-7174 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Differential gene expression analysis of iodide-treated rat thyroid follicular cell line PCCl3.

Leoni S G SG Galante P A PA Ricarte-Filho J C M JC Kimura E T ET

Genomics 20080212 4

The inhibitory effect of supraphysiological iodide concentrations on thyroid hormone synthesis (Wolff-Chaikoff effect) and on thyrocyte proliferation is largely known as iodine autoregulation. However, the molecular mechanisms by which iodide modulates thyroid function remain unclear. In this paper, we analyze the transcriptome profile of the rat follicular cell lineage PCCl3 under untreated and treated conditions with 10(-3) M sodium iodide (NaI). Serial analysis of gene expression (SAGE) revea ...[more]

PMID: 18272324

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Project description:Amiodarone reversibly decreases sodium-iodide symporter mRNA expression at therapeutic concentrations and induces antioxidant responses at supraphysiological concentrations in cultured human thyroid follicles Amiodarone, a potent antiarrhythmic agent, is a highly active oxidant, exerting cytotoxic effects on thyrocytes at pharmacological concentrations. Patients receiving amiodarone usually remain euthyroid, but occasionally develop thyroid dysfunction, such as amiodarone-associated hypothyroidism or amiodarone-induced thyrotoxicosis. To elucidate the mechanism by which amiodarone elicits thyroid dysfunction, human thyroid follicles were cultured with TSH and amiodarone at therapeutic (1-2 microM) and pharmacological (10-20microM) concentrations, and the drug-induced effect on whole human gene expression was analyzed by cDNA microarray. Amiodarone at 1-2microM decreased the expression level of the sodium-iodide symporter (NIS) to nearly half, but did not affect genes participating in thyroid hormonogenesis (thyroid peroxidase, thyroglobulin, pendrin, NADPH oxidase). Higher concentrations (10-20 microM) decreased the expression of all these genes, accompanied by increased expression of antioxidant proteins such as heme oxygenase 1 and ferritin. When thyroid follicles obtained from a patient with Graves’ disease who had been treated with amiodarone for 2 months before thyroidectomy were cultured in amiodarone-free medium, TSH-induced thyroid function was intact, suggesting that amiodarone at a maintenance dose did not elicit any cytotoxic effect on thyrocytes. The ultrastructural features of cultured thyroid follicles were compatible with these in vitro findings. These in vitro and ex vivo findings suggest that patients taking maintenance doses of amiodarone usually remain euthyroid, probably due to escape from the Wolff-Chaikoff effect mediated by decreased expression of NIS mRNA. Furthermore, amiodarone is not cytotoxic for thyrocytes at therapeutic concentrations but elicits cytotoxicity through oxidant activity at supra-physiological concentrations. Keywords: Cultured human thyroid follicles

Dataset Information

Differential gene expression analysis of iodide treated rat thyroid follicular cell line PCCl3

Publications

Differential gene expression analysis of iodide-treated rat thyroid follicular cell line PCCl3.

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