Type 3 iodothyronine deiodinase is expressed in human induced pluripotent stem cell derived cardiomyocytes

Aims: Type 3 iodothyronine deiodinase (D3), which converts thyroxine (T-4) and 3,5,3'- triiodothyronine (T-3) to 3,3',5'-triiodothyronine (rT(3)) and 3,3'-diiodothyronine (T-2), respectively, inactivates thyroid hormones. We investigated the expression and regulation of D3 in human cardiomyocytes which were differentiated from human induced pluripotent stem cells (hiPSCs). Main methods: We characterized D3 activity using liquid chromatography-tandem mass spectrometry (LC-MS/MS)analysis. D3, myosine heavy chain alpha and beta (MHC alpha and beta, respectively), sarcoplasmic reticulum calcium ATPase (SERCA), and phospholamban (PLB) mRNA levels were analyzed by quantitative real-time PCR (qPCR) in hiPSC-derived cardiomyocytes (hiPS-CMs). Key findings: We identified enzyme activity that catalyzes the conversion of T-3 to T-2 in both hiPS-CMs and hiPSCs, which showed characteristics compatible with those for D3. D3 mRNA was identified in these cells using qPCR analysis. T-3 and hypoxia mimetics such as CoCl2 and DFO, increased the D3 mRNA level in both hiPS-CMs and hiPSCs. Addition of iopanoic acid, a competitive inhibitor of iodothyronine deiodination, in the culture medium of hiPS-CMs, increased the mRNA levels such as MHC alpha and beta, SERCA, and PLB induced by T-3. Significants: Our findings indicate that D3 is expressed in hiPS-CMs, and may decrease the intracellular T-3 concentration, and may decrease the expression of cardiac genes such as MHC alpha and beta, SERCA, and PLB in hiPS-CMs.