Type 1 iodothyronine deiodinase in heart --effects of triiodothyronine and angiotensin II on its activity and mRNA in cultured rat myocytes.
We previously demonstrated that iodothyronine 5'-deiodination (5'D) activity is present and increased by triiodothyronine (T3) and angiotensin II (Ang II) in cultured rat cardiac myocytes. To further elucidate the stimulatory mechanism of Ang II, we investigated the effect of intracellular Ca2+ and protein kinase C on myocardial 5'D activity. Moreover, to elucidate the molecular mechanism of the stimulatory effect of T3 and Ang II, we detected the mRNA levels by means of a reverse-transcriptase polymerase chain reaction (RT-PCR). 5'D activity was increased by adding Bay-k 8644, Ca2+ channel agonist and the effect of Bay-k 8644 was completely blocked by nifedipine, a Ca2+ channel antagonist. 12-O-tetradecanoylphorbol-13-acetate, a protein kinase C activator, similarly stimulated 5'D activity. The addition of a high concentration (20-40 mM) of K+, which caused the depolarization of the membrane had significant stimulatory effects on 5'D activity. Type 1 deiodinase (D1) mRNA was evident in myocardial cells by RT-PCR in a single 758 bp band similar to that in the liver. Cardiac fibroblasts did not express the D1 mRNA. A significant increase in D1 mRNA was also evident after adding T3 and Ang II. These findings indicate that 5'D activity in myocardial cells is increased by activating the voltage sensitive Ca2+ channel, protein kinase C, and membrane depolarization, and that the D1 mRNA is present in cardiac myocytes and is increased by T3 and Ang II. This study therefore suggests that Ang II could affect the action of thyroid hormone on the heart by increasing the D1 gene expression.
Yonemoto
T
T
Second Department of Internal Medicine, Kansai Medical University, Moriguchi, Osaka, Japan.
Nishikawa
M
M
Matsubara
H
H
Mori
Y
Y
Toyoda
N
N
Gondou
A
A
Imai
Y
Y
Iwasaka
T
T
Inada
M
M
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects*; D007453:Iodide Peroxidase / Q000235:genetics* / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology*; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology*
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D012333:RNA, Messenger; D014284:Triiodothyronine; D000804:Angiotensin II; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D007453:Iodide Peroxidase; D011493:Protein Kinase C; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium