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Type 2 Iodothyronine Deiodinase Activity Is Required for Rapid Stimulation of PI3K by Thyroxine in Human Umbilical Vein Endothelial Cells
Type 2 Iodothyronine Deiodinase Activity Is Required for Rapid Stimulation of PI3K by Thyroxine in Human Umbilical Vein Endothelial Cells
- Source :
- Endocrinology. 156:4312-4324
- Publication Year :
- 2015
- Publisher :
- The Endocrine Society, 2015.
-
Abstract
- Thyroid hormones (THs) exert a number of physiological effects on the cardiovascular system. Some of the nongenomic actions of T3 are achieved by cross coupling the TH receptor (TR) with the phosphatidylinositol 3-kinase (PI3K)/protein kinase Akt (Akt) pathway. We observed that both T3 and T4 rapidly stimulated Akt phosphorylation and Ras-related C3 botulinum toxin substrate 1 (Rac1) activation, which resulted in cell migration, in a PI3K-dependent manner in human umbilical vein endothelial cells (HUVECs). We identified the expression of type 2 iodothyronine deiodinase (D2), which converts T4 to T3, and TRα1 in HUVECs. D2 activity was significantly stimulated by (Bu)2cAMP in HUVECs. The blockade of D2 activity through transfection of small interfering RNA (siRNA) specific to D2 as well as by addition of iopanoic acid, a potent D2 inhibitor, abolished Akt phosphorylation, Rac activation, and cell migration induced by T4 but not by T3. The inhibition of TRα1 expression by the transfection of siRNA for TRα1 canceled Akt phosphorylation, Rac activation, and cell migration induced by T3 and T4. These findings suggest that conversion of T4 to T3 by D2 is required for TRα1/PI3K-mediated nongenomic actions of T4 in HUVECs, including stimulation of Akt phosphorylation and Rac activation, which result in cell migration.
- Subjects :
- rac1 GTP-Binding Protein
medicine.medical_specialty
Small interfering RNA
RAC1
Iodide Peroxidase
Phosphatidylinositol 3-Kinases
Endocrinology
Cell Movement
Internal medicine
Human Umbilical Vein Endothelial Cells
medicine
Humans
Phosphorylation
RNA, Small Interfering
Protein kinase B
Cells, Cultured
PI3K/AKT/mTOR pathway
Original Research
Phosphoinositide 3-kinase
biology
Thyroxine
Iodothyronine deiodinase
biology.protein
Triiodothyronine
Signal transduction
Proto-Oncogene Proteins c-akt
Signal Transduction
Thyroid Hormone Receptors alpha
Subjects
Details
- ISSN :
- 19457170 and 00137227
- Volume :
- 156
- Database :
- OpenAIRE
- Journal :
- Endocrinology
- Accession number :
- edsair.doi.dedup.....543eb615e30311fa3a2a8f7aab837328
- Full Text :
- https://doi.org/10.1210/en.2014-1988