A novel role for AMP-kinase in the regulation of the Na+/I--symporter and iodide uptake in the rat thyroid gland
| Autor: | Juliana Cazarin, Denise P. Carvalho, Renata L. Araujo, Elaine Cristina Lima de Souza, Rolando B. Ceddia, Bruno Moulin de Andrade, Robert L. S. Perry |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty Physiology Iodide Thyroid Gland Adenylate kinase Thyrotropin Biology Cell Line Thyroid-stimulating hormone Internal medicine medicine Animals Hypoglycemic Agents Enzyme Inhibitors Rats Wistar Protein kinase A chemistry.chemical_classification Sulfonamides Symporters Thyroid Adenylate Kinase Colforsin AMPK Biological Transport Cell Biology Iodides Ribonucleotides Aminoimidazole Carboxamide Isoquinolines Rats Endocrinology medicine.anatomical_structure chemistry Symporter Endocrine gland |
| Zdroj: | American journal of physiology. Cell physiology. 300(6) |
| ISSN: | 1522-1563 |
| Popis: | The aim of this study was to investigate the role of AMP-kinase (AMPK) in the regulation of iodide uptake by the thyroid gland. Iodide uptake was assessed in PCCL3 follicular thyroid cells exposed to the AMPK agonist 5-aminoimidazole-4-carboxamide-ribonucleoside (AICAR), and also in rat thyroid glands 24 h after a single intraperitoneal injection of AICAR. In PCCL3 cells, AICAR-induced AMPK and acetyl-CoA carboxylase (ACC) phosphorylation decreased iodide uptake in a concentration-dependent manner, while the AMPK inhibitor compound C prevented this effect. In the thyroid gland of rats injected with AICAR, AMPK and ACC phosphorylation was increased and iodide uptake was reduced by ∼35%. Under conditions of increased AMPK phosphorylation/activation such as TSH deprivation or AICAR treatment, significant reductions in cellular Na+/I−-symporter (NIS) protein (∼41%) and mRNA content (∼65%) were observed. The transcriptional (actinomycin D) and translational (cycloheximide) inhibitors, as well as the AMPK inhibitor compound C prevented AICAR-induced reduction of NIS protein content in PCCL3 cells. The presence of TSH in the culture medium reduced AMPK phosphorylation in PCCL3 cells, while inhibition of protein kinase A (PKA) with H89 prevented this effect. Conversely, the adenylyl cyclase activator forskolin abolished the AMPK phosphorylation response induced by TSH withdrawal in PCCL3 cells. These findings demonstrate that TSH suppresses AMPK phosphorylation/activation in a cAMP-PKA-dependent manner. In summary, we provide novel evidence that AMPK is involved in the physiological regulation of iodide uptake, which is an essential step for the formation of thyroid hormones as well as for the regulation of thyroid function. |
| Databáze: | OpenAIRE |
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