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Mehdi Rajabi, Murat Yalcin, Shaker A Mousa
In the angiogenesis process, integrins, which are members of a family of cell surface transmembrane receptors, play a critical role particularly in blood vessel formation and the local release of vascular growth factors. Thyroid hormones such as l-thyroxine (T4 ) and 3,5,3'-triiodo-l-thyronine (T3 ) promote angiogenesis and tumor cell proliferation via integrin αvβ3 receptor. At or near an arginine-glycine-aspartate (RGD) recognition site on the binding pocket of integrin αv β3 , tetraiodothyroacetic acid (tetrac, a deaminated derivative of T4 ) is a thyrointegrin receptor antagonist and blocks the actions of T3 and T4 as well as different growth factors-mediated angiogenesis...
February 26, 2018: Bioorganic & Medicinal Chemistry Letters
Kentaro Kasai, Norihito Nishiyama, Kiyoshi Yamauchi
Transthyretin (TTR) is a plasma thyroid hormone (TH) binder that emerged from an ancient hydroxyisourate hydrolase by gene duplication. To know how an ancient TTR had high affinity for THs, molecular and TH binding properties of lamprey TTRs were investigated. In adult serum, the lipoprotein LAL was a major T3 binder with low affinity. Lamprey TTRs had an N-terminal histidine-rich segment, and had two classes of binding sites for 3,3',5-triiodo-L-thyronine (T3): a high-affinity and a low-affinity site. Mutant TTRΔ3-11, lacking the N-terminal histidine-rich segment, lost the high-affinity T3 binding site...
February 27, 2018: Molecular and Cellular Endocrinology
Biran Zhu, Gang Zhao, Lihua Yang, Bingsheng Zhou
Tetrabromobisphenol A (TBBPA), one of the most widely used brominated flame retardants (BFRs), has resulted in worldwide environmental contamination. TBBPA has been reported as a thyroid endocrine disruptor and a potential neurotoxicant. However, the underlying mechanism is still not clear. In this study, zebrafish (Danio rerio) embryos (2 h post-fertilization, hpf) were exposed to different concentrations of TBBPA (50, 100, 200 and 400 μg/L) alone or in combination with 3,3',5-triiodo-l-thyronine (T3, 20 μg/L + TBBPA, 200 μg/L)...
February 1, 2018: Chemosphere
Paul J Davis, Jack L Leonard, Hung-Yun Lin, Matthew Leinung, Shaker A Mousa
Nongenomic actions of thyroid hormone are initiated by the hormone at receptors in the plasma membrane, in cytoplasm, or in mitochondria and do not require the interaction of nuclear thyroid hormone receptors (TRs) with their primary ligand, 3,5,3'-triiodo-l-thyronine (T3). Receptors involved in nongenomic actions may or may not have structural homologies with TRs. Certain nongenomic actions that originate at the plasma membrane may modify the state and function of intranuclear TRs. Reviewed here are nongenomic effects of the hormone-T3 or, in some cases, l-thyroxine (T4)-that are initiated at (a) truncated TRα isoforms, e...
2018: Vitamins and Hormones
Rumi Tanoue, Imari Kume, Yasuo Yamamoto, Kohki Takaguchi, Kei Nomiyama, Shinsuke Tanabe, Tatsuya Kunisue
Thyroid hormones (THs), which mainly consist of 3, 3', 5-triiodo-l-thyronine (T3) and L-thyroxine (T4), play a critical role in regulating biological processes such as growth and metabolism in various animal species. Thus, accurate measurement of T3 and T4, especially physiologically active free (protein-unbound) forms, in serum/plasma is needed for the evaluation of TH homeostasis. However, such high-precision determination of free THs is lacking for non-human species. The present study aimed to develop a highly sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of six free THs in serum/plasma, which is applicable to not only humans but also non-human species...
January 30, 2018: Journal of Chromatography. A
Xiaopeng Chen, Kyla M Walter, Galen W Miller, Pamela J Lein, Birgit Puschner
Environmental toxicants that interfere with thyroid hormone (TH) signaling can impact growth and development in animals and humans. Zebrafish represent a model to study chemically-induced TH disruption, prompting the need for sensitive detection of THs. Simultaneous quantification of 3,3',5-triiodo-L-thyronine (T3), thyroxine (T4), 3,3',5'-triiodo-L-thyronine (rT3), 3,5-diiodo-L-thyronine (3,5-T2), and 3,3'-diiodo-L-thyronine (3,3'-T2) in zebrafish larvae was achieved by ultra-performance liquid chromatography-tandem mass spectrometry in positive ion mode...
January 3, 2018: Biomedical Chromatography: BMC
Chen Weingarten, Yonatan Jenudi, Rami Yair Tshuva, Dotan Moskovich, Adi Alfandari, Aleck Hercbergs, Paul J Davis, Martin Ellis, Osnat Ashur-Fabian
Ovarian cancer is a highly metastatic disease. The metastatic potential is enhanced by epithelial to mesenchymal transition (EMT) in which αvβ3 integrin plays a role. Thyroid hormones (L-thyroxine, T4, and 3,5,3'-triiodo-L-thyronine, T3) bind this integrin, and we hypothesized that the thyroid hormone-αvβ3 axis may be involved in EMT activity in ovarian cancer. The transcription (mRNA), protein abundance (westerns), and protein localization (fluorescence microscopy) of several EMT markers were studied in ovarian cancer cells (OVCAR-3, A2780, and SKOV-3) treated with 1 nM T3 or 100 nM T4 for 1-24 h...
December 19, 2017: Hormones & Cancer
Syuan-Ling Lin, Sheng-Ming Wu, I-Hsiao Chung, Yang-Hsiang Lin, Ching-Ying Chen, Hsiang-Cheng Chi, Tzu-Kang Lin, Chau-Ting Yeh, Kwang-Huei Lin
Thyroid hormone, 3,3',5-triiodo-l-thyronine (T3 ), mediates several physiological processes, including embryonic development, cellular differentiation and cell proliferation, via binding to its nuclear thyroid receptors (TR). Previous microarray and Chromatin immunoprecipitation (ChIP)-on-ChIP analyses have revealed that interferon-stimulated gene 20 kDa (ISG20), an exoribonuclease involved in the antiviral function of interferon, is up-regulated by T3 in HepG2-TR cells. However, the underlying mechanisms of ISG20 action in tumor progression remain unknown to date...
January 2018: Neoplasia: An International Journal for Oncology Research
Alejandro Rodríguez-Molinero, Aleck Hercbergs, Manuel Sarrias, Antonio Yuste
Preclinical studies have attributed 3,3',5-triiodo-L-thyronine (T3) a direct negative effect on tumor progression, as well as chemosensitizing, differentiating and immunomodulatory properties. On the other hand, L-thyroxine (T4), via a thyroid hormone receptor on plasma membrane integrin αvβ3, promotes solid tumor growth and neoangiogenesis, therefore lowering endogenous T4 reduces tumor growth rate. We present the case of two patients with metastatic triple negative breast cancer and metastatic pancreatic cancer respectively, who benefit of the sole treatment with antithyroid drugs and exogenous administration of T3 (liothyronine)...
November 3, 2017: Cancer Biomarkers: Section A of Disease Markers
Bin Lin, Xianming Lin, Maxine Stachel, Elisha Wang, Yumei Luo, Joshua Lader, Xiaofang Sun, Mario Delmar, Lei Bu
With recent advances in stem cell technology, it is becoming efficient to differentiate human pluripotent stem cells (hPSCs) into cardiomyocytes, which can subsequently be used for myriad purposes, ranging from interrogating mechanisms of cardiovascular disease, developing novel cellular therapeutic approaches, as well as assessing the cardiac safety profile of compounds. However, the relative inability to acquire abundant pure and mature cardiomyocytes still hinders these applications. Recently, it was reported that glucose-depleted culture medium supplemented with lactate can facilitate purification of hPSC-derived cardiomyocytes...
2017: Frontiers in Endocrinology
Keren Cohen, Uri Abadi, Aleck Hercbergs, Paul J Davis, Martin Ellis, Osnat Ashur-Fabian
Multiple myeloma (MM) is a plasma cell malignancy in which involvement of the thyroid hormone-integrin αvβ3 pathway was shown and pharmacologic inhibition of this pathway is a rational approach to disease management. A thyroid hormone derivative, tetraiodothyroacetic acid (tetrac), which inhibits L-thyroxine (T4) and 3,5,3'-triiodo-L-thyronine (T3) binding to αvβ3 integrin, was studied in five MM cell lines and primary bone marrow (BM) MM cells. Tetrac inhibited MM cell proliferation (absolute cell number/viability) and induced caspase-dependent apoptosis (annexin-V/PI and cell cycle)...
October 10, 2017: Endocrine-related Cancer
Shan S Parikh, Daniel J Blackwell, Nieves Gomez-Hurtado, Michael Frisk, Lili Wang, Kyungsoo Kim, Christen P Dahl, Arnt Fiane, Theis Tønnessen, Dmytro O Kryshtal, William E Louch, Bjorn C Knollmann
RATIONALE: Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are increasingly being used for modeling heart disease and are under development for regeneration of the injured heart. However, incomplete structural and functional maturation of hiPSC-CM, including lack of T-tubules, immature excitation-contraction coupling, and inefficient Ca-induced Ca release remain major limitations. OBJECTIVE: Thyroid and glucocorticoid hormones are critical for heart maturation...
December 8, 2017: Circulation Research
Rosalba Senese, Federica Cioffi, Pieter de Lange, Cristina Leanza, Liliana F Iannucci, Elena Silvestri, Maria Moreno, Assunta Lombardi, Fernando Goglia, Antonia Lanni
3,3',5-triiodo-L-thyronine (T3) improves hepatic lipid accumulation by increasing lipid catabolism but it also increases lipogenesis, which at first glance appears contradictory. Recent studies have shown that 3,5-diiodothyronine (T2), a natural thyroid hormone derivative, also has the capacity to stimulate hepatic lipid catabolism, however, little is known about its possible effects on lipogenic gene expression. Because genes classically involved in hepatic lipogenesis such as SPOT14, acetyl-CoA-carboxylase (ACC), and fatty acid synthase (FAS) contain thyroid hormone response elements (TREs), we studied their transcriptional regulation, focusing on TRE-mediated effects of T3 compared to T2 in rats receiving high-fat diet (HFD) for 1 week...
2017: Frontiers in Physiology
Malik Muhammad Abdullah, Anurag, Zoltan Jurek, Sang-Kil Son, Robin Santra
When matter is exposed to a high-intensity x-ray free-electron-laser pulse, the x rays excite inner-shell electrons leading to the ionization of the electrons through various atomic processes and creating high-energy-density plasma, i.e., warm or hot dense matter. The resulting system consists of atoms in various electronic configurations, thermalizing on subpicosecond to picosecond timescales after photoexcitation. We present a simulation study of x-ray-heated solid-density matter. For this we use XMDYN, a Monte Carlo molecular-dynamics-based code with periodic boundary conditions, which allows one to investigate nonequilibrium dynamics...
August 2017: Physical Review. E
Atsuko Ishizuya-Oka
During Xenopus metamorphosis, most tadpole organs remodel from the larval to adult form to prepare for adaptation to terrestrial life. Organ culture serves as an important tool for studying larval-to-adult organ remodeling independent of the effects of other parts of the body. Here, I introduce a protocol for organ culture in vitro using the Xenopus laevis tadpole intestine before metamorphic climax. During culture in the absence of exogenous 3,3',5-triiodo-l-thyronine (T3), the most potent natural thyroid hormone, the intestine remains in its larval state without any metamorphic changes...
September 14, 2017: Cold Spring Harbor Protocols
Elena Shinderman-Maman, Chen Weingarten, Dotan Moskovich, Haim Werner, Aleck Hercbergs, Paul J Davis, Martin Ellis, Osnat Ashur-Fabian
The regulation of cancer-relevant genes by the thyroid hormones, 3, 5, 3'-Triiodo-L-thyronine (T3) and L-thyroxine (T4), was recently acknowledged. However, limited data exists on the hormonal effects on gene expression in ovarian cancer, a gynecological malignancy associated with a low cure rate. The expression of fifteen genes involved in DNA repair, cell cycle, apoptosis, and tumor suppression was evaluated in OVCAR-3 and A2780 cell lines, using real-time PCR following short incubation with T3 (1 nM) or T4 (100 nM)...
January 2018: Molecular Carcinogenesis
Xin Ru Deng, Lin Ding, Tian Ge Wang, Min Xu, Jie Li Lu, Mian Li, Zhi Yun Zhao, Yu Hong Chen, Yu Fang Bi, Yi Ping Xu, Yu Xu
Serum fetuin-A levels are reportedly elevated in hyperthyroidism. However, there are few relevant epidemiologic studies. We conducted a cross-sectional study in Songnan community, China in 2009 to investigate the association between serum fetuin-A concentrations and thyroid function. A total of 2,984 participants aged 40 years and older were analyzed. Multivariable linear regression analysis revealed that serum fetuin-A concentra- tions were positively associated with log (free triiodothyronine) and were inversely associated with log (thyroid peroxidase antibody) after adjustment (both P < 0...
June 2017: Biomedical and Environmental Sciences: BES
Amedeo Columbano, Grazia Chiellini, Marta Anna Kowalik
Thyroid hormones (THs), namely, 3,5,3'-triiodo-l-thyronine (T3) and 3,5,3',5'-tetraiodo-l-thyronine (thyroxine or T4), influence a variety of physiological processes that have important implications in fetal development, metabolism, cell growth, and proliferation. While THs elicit several beneficial effects on lipid metabolism and improve myocardial contractility, these therapeutically desirable effects are associated to a thyrotoxic state that severely limits the possible use of THs as therapeutic agents. Therefore, several efforts have been made to develop T3 analogs that could retain the beneficial actions (triglyceride, cholesterol, obesity, and body mass lowering) without the adverse TH-dependent side effects...
November 27, 2017: Gene Expression
Tetsu Hatsukano, Junko Kurisu, Kansai Fukumitsu, Kazuto Fujishima, Mineko Kengaku
Thyroid hormone 3,3',5-Triiodo-L-thyronine (T3) is essential for proper brain development. Perinatal loss of T3 causes severe growth defects in neurons and glia, including strong inhibition of dendrite formation in Purkinje cells in the cerebellar cortex. Here we show that T3 promotes dendritic outgrowth of Purkinje cells through induction of peroxisome proliferator-activated receptor gamma (PPARγ) co-activator 1α (PGC-1α), a master regulator of mitochondrial biogenesis. PGC-1α expression in Purkinje cells is upregulated during dendritic outgrowth in normal mice, while it is significantly retarded in hypothyroid mice or in cultures depleted of T3...
2017: Frontiers in Cellular Neuroscience
Viswanathan Rajagopalan, Youhua Zhang, Christine Pol, Clifford Costello, Samantha Seitter, Ann Lehto, Olga V Savinova, Yue-Feng Chen, A Martin Gerdes
Background: We have shown that thyroid hormones (THs) are cardioprotective and can be potentially used as safe therapeutic agents for diabetic cardiomyopathy and permanent infarction. However, no reliable, clinically translatable protocol exists for TH treatment of myocardial ischemia-reperfusion (IR) injury. We hypothesized that modified low-dose triiodo-L-thyronine (T3) therapy would confer safe therapeutic benefits against IR injury. Methods: Adult female rats underwent left coronary artery ligation for 60 min or sham surgeries...
2017: Frontiers in Physiology
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