Substantial impact of 3-iodothyronamine (T1AM) on the regulations of fluorescent thermoprobe-measured cellular temperature and natriuretic peptide expression in cardiomyocytes
Abstract There is growing interest in 3-iodothyronamine (T1AM), an active thyroid hormone metabolite, that induces negative inotropic and chronotropic actions in the heart and exerts systemic hypothermic action. We explored the direct impact of T1AM on cardiomyocytes with a focus on the regulation o...
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| Format: | Article |
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Nature Portfolio
2022-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-17086-2 |
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| author | Hirotake Takahashi Tomohisa Nagoshi Haruka Kimura Yoshiro Tanaka Rei Yasutake Yuhei Oi Akira Yoshii Toshikazu D. Tanaka Yusuke Kashiwagi Michihiro Yoshimura |
| author_facet | Hirotake Takahashi Tomohisa Nagoshi Haruka Kimura Yoshiro Tanaka Rei Yasutake Yuhei Oi Akira Yoshii Toshikazu D. Tanaka Yusuke Kashiwagi Michihiro Yoshimura |
| author_sort | Hirotake Takahashi |
| collection | DOAJ |
| description | Abstract There is growing interest in 3-iodothyronamine (T1AM), an active thyroid hormone metabolite, that induces negative inotropic and chronotropic actions in the heart and exerts systemic hypothermic action. We explored the direct impact of T1AM on cardiomyocytes with a focus on the regulation of the intracellular temperature and natriuretic peptide (NP) expression. A thermoprobe was successfully introduced into neonatal rat cardiomyocytes, and the temperature-dependent changes in the fluorescence intensity ratio were measured using a fluorescence microscope. After one-hour incubation with T1AM, the degree of change in the fluorescence intensity ratio was significantly lower in T1AM-treated cardiomyocytes than in equivalent solvent-treated controls (P < 0.01), indicating the direct hypothermic action of T1AM on cardiomyocytes. Furthermore, T1AM treatment upregulated B-type NP (BNP) gene expression comparable to treatment with endothelin-1 or phenylephrine. Of note, ERK phosphorylation was markedly increased after T1AM treatment, and inhibition of ERK phosphorylation by an MEK inhibitor completely cancelled both T1AM-induced decrease in thermoprobe-measured temperature and the increase in BNP expression. In summary, T1AM decreases fluorescent thermoprobe-measured temperatures (estimated intracellular temperatures) and increases BNP expression in cardiomyocytes by activating the MEK/ERK pathway. The present findings provide new insight into the direct myocardial cellular actions of T1AM in patients with severe heart failure. |
| first_indexed | 2024-04-14T07:40:31Z |
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| id | doaj.art-965f0650519b40af858c4909d9b25bbd |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-14T07:40:31Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-965f0650519b40af858c4909d9b25bbd2022-12-22T02:05:31ZengNature PortfolioScientific Reports2045-23222022-07-011211910.1038/s41598-022-17086-2Substantial impact of 3-iodothyronamine (T1AM) on the regulations of fluorescent thermoprobe-measured cellular temperature and natriuretic peptide expression in cardiomyocytesHirotake Takahashi0Tomohisa Nagoshi1Haruka Kimura2Yoshiro Tanaka3Rei Yasutake4Yuhei Oi5Akira Yoshii6Toshikazu D. Tanaka7Yusuke Kashiwagi8Michihiro Yoshimura9Division of Cardiology, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cardiology, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cardiology, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cardiology, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cardiology, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cardiology, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cardiology, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cardiology, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cardiology, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cardiology, Department of Internal Medicine, The Jikei University School of MedicineAbstract There is growing interest in 3-iodothyronamine (T1AM), an active thyroid hormone metabolite, that induces negative inotropic and chronotropic actions in the heart and exerts systemic hypothermic action. We explored the direct impact of T1AM on cardiomyocytes with a focus on the regulation of the intracellular temperature and natriuretic peptide (NP) expression. A thermoprobe was successfully introduced into neonatal rat cardiomyocytes, and the temperature-dependent changes in the fluorescence intensity ratio were measured using a fluorescence microscope. After one-hour incubation with T1AM, the degree of change in the fluorescence intensity ratio was significantly lower in T1AM-treated cardiomyocytes than in equivalent solvent-treated controls (P < 0.01), indicating the direct hypothermic action of T1AM on cardiomyocytes. Furthermore, T1AM treatment upregulated B-type NP (BNP) gene expression comparable to treatment with endothelin-1 or phenylephrine. Of note, ERK phosphorylation was markedly increased after T1AM treatment, and inhibition of ERK phosphorylation by an MEK inhibitor completely cancelled both T1AM-induced decrease in thermoprobe-measured temperature and the increase in BNP expression. In summary, T1AM decreases fluorescent thermoprobe-measured temperatures (estimated intracellular temperatures) and increases BNP expression in cardiomyocytes by activating the MEK/ERK pathway. The present findings provide new insight into the direct myocardial cellular actions of T1AM in patients with severe heart failure.https://doi.org/10.1038/s41598-022-17086-2 |
| spellingShingle | Hirotake Takahashi Tomohisa Nagoshi Haruka Kimura Yoshiro Tanaka Rei Yasutake Yuhei Oi Akira Yoshii Toshikazu D. Tanaka Yusuke Kashiwagi Michihiro Yoshimura Substantial impact of 3-iodothyronamine (T1AM) on the regulations of fluorescent thermoprobe-measured cellular temperature and natriuretic peptide expression in cardiomyocytes Scientific Reports |
| title | Substantial impact of 3-iodothyronamine (T1AM) on the regulations of fluorescent thermoprobe-measured cellular temperature and natriuretic peptide expression in cardiomyocytes |
| title_full | Substantial impact of 3-iodothyronamine (T1AM) on the regulations of fluorescent thermoprobe-measured cellular temperature and natriuretic peptide expression in cardiomyocytes |
| title_fullStr | Substantial impact of 3-iodothyronamine (T1AM) on the regulations of fluorescent thermoprobe-measured cellular temperature and natriuretic peptide expression in cardiomyocytes |
| title_full_unstemmed | Substantial impact of 3-iodothyronamine (T1AM) on the regulations of fluorescent thermoprobe-measured cellular temperature and natriuretic peptide expression in cardiomyocytes |
| title_short | Substantial impact of 3-iodothyronamine (T1AM) on the regulations of fluorescent thermoprobe-measured cellular temperature and natriuretic peptide expression in cardiomyocytes |
| title_sort | substantial impact of 3 iodothyronamine t1am on the regulations of fluorescent thermoprobe measured cellular temperature and natriuretic peptide expression in cardiomyocytes |
| url | https://doi.org/10.1038/s41598-022-17086-2 |
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