Recovery of 3-Iodothyronamine and Derivatives in Biological Matrixes: Problems and Pitfalls

Lorenzini, Leonardo; Ghelardoni, Sandra; Sacripanti, Ginevra; Chiellini, Grazia; Zucchi, Riccardo

doi:10.1089/thy.2017.0111

Cited by 14 publications

(13 citation statements)

References 24 publications

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“…Previous studies have indicated that 3-T1AM is an effective metabolite product of the TH that can decrease the heart rate and lower the cardiac output [ 16 – 18 ]. We speculated that cardiomyocytes would be an essential target site for 3-T1AM.…”

Section: Discussionmentioning

confidence: 99%

Comparative Transcriptome Analysis Reveals the Potential Cardiovascular Protective Targets of the Thyroid Hormone Metabolite 3-Iodothyronamine (3-T1AM)

Zhou

Zhang

et al. 2020

BioMed Research International

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Background. The thyroid hormone metabolite 3-iodothyronamine (3-T1AM) is rapidly emerging as a promising compound in decreasing the heart rate and lowering the cardiac output. The aim of our study was to fully understand the molecular mechanism of 3-T1AM on cardiomyocytes and its potential targets in cardiovascular diseases. Materials and Methods. In our study, we utilized RNA-Seq to characterize the gene expression in H9C2 cells after 3-T1AM treatment. Comparative transcriptome analysis, including gene ontology, signaling pathways, disease connectivity analysis, and protein-protein interaction networks (PPI), was presented to find the critical gene function, hub genes, and related pathways. Results. A total of 1494 differently expressed genes (DEGs) were identified (192 upregulated and 1302 downregulated genes) in H9C2 cells for 3-T1AM treatment. Of these, 90 genes were associated with cardiovascular diseases. The PPI analysis indicated that 5 hub genes might be the targets of 3-T1AM. Subsequently, eight DEGs characterized using RNA-Seq were confirmed by RT-qPCR assays. Conclusions. Our study provides a comprehensive analysis of 3-T1AM on H9C2 cells and delineates a new insight into the therapeutic intervention of 3-T1AM for the cardiovascular diseases.

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Section: Discussionmentioning

confidence: 99%

Comparative Transcriptome Analysis Reveals the Potential Cardiovascular Protective Targets of the Thyroid Hormone Metabolite 3-Iodothyronamine (3-T1AM)

Zhou

Zhang

et al. 2020

BioMed Research International

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“…In contrast, analysis of 3-T1AM content of various tissues of rodents in several laboratories revealed remarkably high 3-T1AM concentrations in selected tissues, which might even approach those of tissue T4 and T3. The analytical issues related to this challenging task to determine circulating 3-T1AM concentrations have been addressed and discussed in several publications and recent reviews [6,7,18,79]. Apart from method-related issues (not yet solved) several hypotheses have been proposed to explain why 3-T1AM determination in blood of humans or animal experimental models has not revealed a uniform agreement.…”

Section: Biosynthesis Of 35-t2 and 3-t1am From Thm Precursors In Hummentioning

confidence: 99%

Endocrine, Metabolic and Pharmacological Effects of Thyronamines (TAM), Thyroacetic Acids (TA) and Thyroid Hormone Metabolites (THM) – Evidence from in vitro, Cellular, Experimental Animal and Human Studies

Homuth

Lietzow

Schanze

et al. 2020

Exp Clin Endocrinol Diabetes

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Thyroid hormone metabolites (THM) with few or no iodine substituents such as 3,5-T2, the thyronamines 3-T1AM and T0AM, and their oxidation products, the thyroacetic acids (TA) formed by monoamine oxidases, have recently attracted major interest due to their metabolic actions which are in part distinct from those of the classical thyromimetic hormone T3, the major ligand of T3 receptors. This review compiles and discusses in vitro effects of 3,5-T2, TAM and TA reported for thyrocytes, pancreatic islets and hepatocytes as well as findings from in vivo studies in mouse models after single or repeated administration of pharmacological doses of these agents. Comparison of the 3,5-T2 effects on the transcriptome with not yet published proteome data in livers of obese mice on high fat diet indicate a distinct anti-steatotic effect of this THM. Furthermore, uptake, metabolism, and cellular actions via various receptors such as trace amine-associated receptors (TAAR), alpha-adrenergic, GPCR and T3 receptors are discussed. Studies on postulated pathways of biosynthesis of 3-T1AM, its effects on the HPT-axis and thyroid gland as well as insulin secretion are reviewed. 3-T1AM also acts on hepatocytes and interferes with TRPM8-dependent signaling in human cell lines related to the eye compartment. Human studies are presented which address potential biosynthesis routes of 3,5-T2 and 3-T1AM from THM precursors, especially T3. The current state of diagnostic analytics of these minor THM in human blood is portrayed comparing and critically discussing the still divergent findings based on classical immunoassay and recently developed liquid-chromatography/mass- spectrometry methods, which allow quantification of the thyronome spectrum from one single small volume serum sample. The clinical perspectives of use and potential abuse of these biologically active THM is addressed.

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“…Previous studies have indicated that T1AM is an effective metabolite products of the TH that can decrease heart rate, lower cardiac output, and lower body temperature [19][20][21]. The effects of T1AM via TAAR1/TAAR2 at nanomolar concentrations were reported.…”

Section: Discussionmentioning

confidence: 99%

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

Zhou

Liu

2020

Med Sci Monit

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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/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, PPARa, Akt, and GCK and the protein levels of PPARa, 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.

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Recovery of 3-Iodothyronamine and Derivatives in Biological Matrixes: Problems and Pitfalls

Abstract: These results suggest binding and sequestration of T1AM and/or its aldehyde derivative by blood and tissue proteins, with significant isotope effects. These issues might account for the technical problems complicating the analytical assays of endogenous T1AM.

Cited by 14 publications

References 24 publications

Comparative Transcriptome Analysis Reveals the Potential Cardiovascular Protective Targets of the Thyroid Hormone Metabolite 3-Iodothyronamine (3-T1AM)

Comparative Transcriptome Analysis Reveals the Potential Cardiovascular Protective Targets of the Thyroid Hormone Metabolite 3-Iodothyronamine (3-T1AM)

Endocrine, Metabolic and Pharmacological Effects of Thyronamines (TAM), Thyroacetic Acids (TA) and Thyroid Hormone Metabolites (THM) – Evidence from in vitro, Cellular, Experimental Animal and Human Studies

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

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