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12 March 2020 : Laboratory Research  

Thyroid Hormone Metabolite 3-Iodothyronamine (T1AM) Alleviates Hypoxia/Reoxygenation-Induced Cardiac Myocyte Apoptosis via Akt/FoxO1 Pathway

Haiyan Zhou1ABCDE, Bailong Hu2AC, Xingde Liu13ABEFG*

DOI: 10.12659/MSM.923195

Med Sci Monit 2020; 26:e923195


BACKGROUND: The thyroid hormone metabolite 3-iodothyronamine (T1AM) is rapidly emerging as promising compound of decreasing heart rate and lowering cardiac output. The aim of our study was to fully understand the molecular mechanism of T1AM on cardiomyocytes and its potential targets in cardiovascular diseases.

MATERIAL AND METHODS: We developed an in vitro myocardial ischemia-reperfusion injury model of AC-16 cells by hypoxia-reoxygenation injury. Cell viability of AC-16 cells was detected using CCK-8 assay and apoptosis was detected by flow cytometry. RNA-seq was used to characterize the gene expression in H/R-induced AC-16 cells after T1AM treatment. The mRNA levels of FoxO1, PPARα, Akt, and GCK and the protein levels of PPARα, GCK, and components of the Akt/FoxO1 pathway were detected by qRT-PCR and Western blotting, respectively.

RESULTS: Exogenous T1AM increased the H/R-induced AC-16 cell viability in a relatively low concentration. A total of 210 DEGs, including 142 upregulated and 68 downregulated genes, were determined in H/R-induced AC-16 cells treated with or without T1AM. A Venn diagram showed 135 common DEGs. The FoxO signaling pathway was identified via KEGG enrichment analysis of these 135 DEGs. Moreover, T1AM mediated hypometabolism and reduced the apoptosis of H/R-induced AC-16 cells via the Akt/FoxO1 pathway.

CONCLUSIONS: Exogenous T1AM protects against cell injury induced by H/R in AC-16 cells via regulation of the FoxO signaling pathway. Our results suggest that T1AM can play a preventive role in myocardial H/R injury and also provide new insight for clinical management of AMI patients.

Keywords: Apoptosis, Cell Hypoxia, Myocytes, Cardiac, Cell Line, Cell Survival, Forkhead Box Protein O1, Myocardial Infarction, Myocardial Reperfusion Injury, Proto-Oncogene Proteins c-akt, Thyronines



01 October 2022 : Editorial  

Editorial: Rebound COVID-19 and Cessation of Antiviral Treatment for SARS-CoV-2 with Paxlovid and Molnupiravir

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.938532

Med Sci Monit 2022; 28:e938532


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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750