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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

Authors :
Makoto Nara
Hiroyuki Sumino
Takayuki Ogiwara
Osamu Araki
Takao Kimura
Tomoyuki Aoki
Katsuhiko Tsunekawa
Masami Murakami
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.

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