PMID- 21389275
OWN - NLM
STAT- MEDLINE
DCOM- 20110826
LR  - 20200930
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 300
IP  - 6
DP  - 2011 Jun
TI  - A novel role for AMP-kinase in the regulation of the Na+/I--symporter and iodide 
      uptake in the rat thyroid gland.
PG  - C1291-7
LID - 10.1152/ajpcell.00136.2010 [doi]
AB  - 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.
FAU - Andrade, Bruno M
AU  - Andrade BM
AD  - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de 
      Janeiro, Rio de Janeiro, Brazil.
FAU - Araujo, Renata L
AU  - Araujo RL
FAU - Perry, Robert L S
AU  - Perry RL
FAU - Souza, Elaine C L
AU  - Souza EC
FAU - Cazarin, Juliana M
AU  - Cazarin JM
FAU - Carvalho, Denise P
AU  - Carvalho DP
FAU - Ceddia, Rolando B
AU  - Ceddia RB
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110309
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Iodides)
RN  - 0 (Isoquinolines)
RN  - 0 (Ribonucleotides)
RN  - 0 (Sulfonamides)
RN  - 0 (Symporters)
RN  - 1F7A44V6OU (Colforsin)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - 4XE5NDT4K1 (sodium-iodide symporter)
RN  - 9002-71-5 (Thyrotropin)
RN  - EC 2.7.4.3 (Adenylate Kinase)
RN  - F0X88YW0YK (AICA ribonucleotide)
RN  - M876330O56 (N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide)
SB  - IM
MH  - Adenylate Kinase/antagonists & inhibitors/*metabolism
MH  - Aminoimidazole Carboxamide/analogs & derivatives/pharmacology
MH  - Animals
MH  - Biological Transport/physiology
MH  - Cell Line
MH  - Colforsin/metabolism
MH  - Enzyme Inhibitors/metabolism
MH  - Hypoglycemic Agents/pharmacology
MH  - Iodides/*metabolism
MH  - Isoquinolines/metabolism
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - Ribonucleotides/pharmacology
MH  - Sulfonamides/metabolism
MH  - Symporters/*metabolism
MH  - Thyroid Gland/cytology/drug effects/*metabolism
MH  - Thyrotropin/metabolism
EDAT- 2011/03/11 06:00
MHDA- 2011/08/30 06:00
CRDT- 2011/03/11 06:00
PHST- 2011/03/11 06:00 [entrez]
PHST- 2011/03/11 06:00 [pubmed]
PHST- 2011/08/30 06:00 [medline]
AID - ajpcell.00136.2010 [pii]
AID - 10.1152/ajpcell.00136.2010 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2011 Jun;300(6):C1291-7. doi: 
      10.1152/ajpcell.00136.2010. Epub 2011 Mar 9.