scholarly journals Identification and Functional Characterization of Zebrafish Solute Carrier Slc16a2 (Mct8) as a Thyroid Hormone Membrane Transporter

Endocrinology ◽  
2011 ◽  
Vol 152 (12) ◽  
pp. 5065-5073 ◽  
Author(s):  
Francisco J. Arjona ◽  
Erik de Vrieze ◽  
Theo J. Visser ◽  
Gert Flik ◽  
Peter H. M. Klaren
Keyword(s):  
Thyroid Hormone ◽  
Functional Characterization ◽  
Proteolytic Processing ◽  
The Body ◽  
Membrane Transporters ◽  
Monocarboxylate Transporter ◽  
Independent Manner ◽  
Organ Systems ◽  
Solute Carrier ◽  
Cloned Cdna

Most components of the thyroid system in bony fish have been described and characterized, with the notable exception of thyroid hormone membrane transporters. We have cloned, sequenced, and expressed the zebrafish solute carrier Slc16a2 (also named monocarboxylate transporter Mct8) cDNA and established its role as a thyroid hormone transport protein. The cloned cDNA shares 56–57% homology with its mammalian orthologs. The 526-amino-acid sequence contains 12 predicted transmembrane domains. An intracellular N-terminal PEST domain, thought to be involved in proteolytic processing of the protein, is present in the zebrafish sequence. Measured at initial rate and at the body/rearing temperature of zebrafish (26 C), T3 uptake by zebrafish Slc16a2 is a saturable process with a calculated Michaelis-Menten constant of 0.8 μM T3. The rate of T3 uptake is temperature dependent and Na+ independent. Interestingly, at 26 C, zebrafish Slc16a2 does not transport T4. This implies that at a normal body temperature in zebrafish, Slc16a2 protein is predominantly involved in T3 uptake. When measured at 37 C, zebrafish Slc16a2 transports T4 in a Na+-independent manner. In adult zebrafish, the Slc16a2 gene is highly expressed in brain, gills, pancreas, liver, pituitary, heart, kidney, and gut. Beginning from the midblastula stage, Slc16a2 is also expressed during zebrafish early development, the highest expression levels occurring 48 h after fertilization. This is the first direct evidence for thyroid hormone membrane transporters in fish. We suggest that Slc16a2 plays a key role in the local availability of T3 in adult tissues as well as during the completion of morphogenesis of primary organ systems.

scholarly journals Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Enrico Girardi ◽  
Gennaro Agrimi ◽  
Ulrich Goldmann ◽  
Giuseppe Fiume ◽  
Sabrina Lindinger ◽  
...  
Keyword(s):  
Mitochondrial Respiration ◽  
Genetic Interaction ◽  
Functional Characterization ◽  
Membrane Transporters ◽  
Genetic Interactions ◽  
Functional Information ◽  
Carrier Proteins ◽  
Mitochondrial Import ◽  
Redox Metabolism ◽  
Solute Carrier

AbstractAbout a thousand genes in the human genome encode for membrane transporters. Among these, several solute carrier proteins (SLCs), representing the largest group of transporters, are still orphan and lack functional characterization. We reasoned that assessing genetic interactions among SLCs may be an efficient way to obtain functional information allowing their deorphanization. Here we describe a network of strong genetic interactions indicating a contribution to mitochondrial respiration and redox metabolism for SLC25A51/MCART1, an uncharacterized member of the SLC25 family of transporters. Through a combination of metabolomics, genomics and genetics approaches, we demonstrate a role for SLC25A51 as enabler of mitochondrial import of NAD, showcasing the potential of genetic interaction-driven functional gene deorphanization.

scholarly journals THYROID HORMONE CELL-MEMBRANE TRANSPORTERS DEFECT: A NOVEL GENETIC SYNDROME OF THYROID HORMONE RESISTANCE

2014 ◽  
Vol 2 (1) ◽  
Author(s):  
Mateus Fernandes Da Silva Medeiros ◽  
Helton Estrela Ramos
Keyword(s):  
Thyroid Hormone ◽  
Membrane Transporters ◽  
Monocarboxylate Transporter ◽  
Target Cells ◽  
Hormone Resistance ◽  
Genetic Syndrome ◽  
Serum T4 ◽  
Thyroid Hormone Levels ◽  
Low Serum

Many studies has confirmed the crucial role of thyroid hormone transporters for TH action in human target cells. The importance was better understood by observing the phenotype in patients harboring mutations of the monocarboxylate transporter 8 (MCT8) gene immediately linked to Allan Herndon-Dudley Syndrome (AHDS), in which severe neurological findings are associated with abnormal Thyroid hormone levels. The disease is X-chromossome linked, with males presenting a homogeneous neurological psychomotor phenotype and mental retardation associated with low serum T4 and elevated T3 levels. The mechanism of disease is still obscure and either the physiopathology as the existent therapeutic options need to be better studied.

scholarly journals Functional Characterization of Xenopus Thyroid Hormone Transporters mct8 and oatp1c1

Endocrinology ◽  
2017 ◽  
Vol 158 (8) ◽  
pp. 2694-2705 ◽  
Author(s):  
Bilal B Mughal ◽  
Michelle Leemans ◽  
Elaine C Lima de Souza ◽  
Sébastien le Mevel ◽  
Petra Spirhanzlova ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Quantitative Polymerase Chain Reaction ◽  
Organic Anion ◽  
Expression Patterns ◽  
Functional Characterization ◽  
Monocarboxylate Transporter ◽  
Protein Alignment ◽  
Specific Expression ◽  
Bootstrap Analysis ◽  
Active Efflux

Abstract Xenopus is an excellent model for studying thyroid hormone signaling as it undergoes thyroid hormone–dependent metamorphosis. Despite the fact that receptors and deiodinases have been described in Xenopus, membrane transporters for these hormones are yet to be characterized. We cloned Xenopus monocarboxylate transporter 8 (mct8) and organic anion-transporting polypeptide 1C1 (oatpc1c1), focusing on these two transporters given their importance for vertebrate brain development. Protein alignment and bootstrap analysis showed that Xenopus mct8 and oatp1c1 are closer to their mammalian orthologs than their teleost counterparts. We functionally characterized the two transporters using a radiolabeled hormones in vitro uptake assay in COS-1 cells. Xenopus mct8 was found to actively transport both T3 and T4 bidirectionally. As to the thyroid precursor molecules, diiodotyrosine (DIT) and monoiodotyrosine (MIT), both human and Xenopus mct8, showed active efflux, but no influx. Again similar to humans, Xenopus oatp1c1 transported T4 but not T3, MIT, or DIT. We used reverse transcription quantitative polymerase chain reaction and in situ hybridization to characterize the temporal and spatial expression of mct8 and oatp1c1 in Xenopus. Specific expression of the transporter was observed in the brain, with increasingly strong expression as development progressed. In conclusion, these results show that Xenopus thyroid hormone transporters are functional and display marked spatiotemporal expression patterns. These features make them interesting targets to elucidate their roles in determining thyroid hormone availability during embryonic development.

Perbedaan Efektivitas Pemberian Origami Dan Playdough Terhadap Perkembangan Pada Anak Prasekolah Kelompok A Di TK Aisyiyah Bustanul Athfal Kota Kediri

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Halimatus Saidah ◽  
Yunida Septiyanty
Keyword(s):  
Child Development ◽  
Sampling Technique ◽  
The Body ◽  
Purposive Sampling ◽  
Organ Systems ◽  
Post Test ◽  
Group A ◽  
Key Words Development ◽  
Children Development ◽  
Research Show

ABSTRAKPerkembangan (development) adalah bertambahnya kemampuan atau fungsi semua sistem organ tubuh sebagai akibat bertambahnya kematangan atau maturitas fungsi sistem organ tubuh (Dewi, 2013). Tujuan penelitian ini adalah mengetahui perbedaan efektivitas pemberian origami dan playdough terhadap perkembangan pada anak prasekolah kelompok A di TK Aisyiyah Bustanul Athfal tahun 2018.Desain penelitian yang digunakan adalah penelitian pre eksperiment dengan pendekatan pre-test and post-test Design. Populasi yang diteliti adalah seluruh anak kelompok A di TK Aisyiyah Bustanul Athfal berjumlah 56 anak dengan teknik purposive sampling diperoleh sampel 36 responden. Instrumen penelitian yang digunakan adalah lembar KPSP. Hasil penelitian kemudian dianalisa dengan menggunakan wilcoxon signed rank.Hasil penelitian yang dilakukan menunjukan bahwa perkembangan anak sebelum pelaksanaan pemberian Origami didapatkan setengahnya perkembangan anak meragukan, setelah pelaksanaan didapatkan hampir seluruhnya perkembangan anak sesuai. Perkembangan anak sebelum pelaksanaan pemberian Playdough didapatkan sebagian besar perkembangan anak meragukan, setelah pelaksanaan didapatkan sebagian besar perkembangan anak sesuai. Hasil analisis menunjukkan ada pengaruh pemberian permainan origami dan permainan Playdough terhadap perkembangan anak kelompok A di TK Aisyiyah Bustanul Athfal Tahun 2018 dengan hasil ρ-value = 0,001 ɑ = 0,05 dari kelompok origami dan ρ-value = 0,007 ɑ = 0,05 dari kelompok playdough, sedangkan hasil analisis perbedaan adanya perbedaan efektivitas pengaruh pemberian permainan origami dan playdough terhadap perkembangan anak pada kelompok A di TK Aisyiyah Bustanul Athfal Tahun 2018 dengan hasil ρ-value = 0,043 ɑ = 0,05.Berdasarkan hasil penelitian dapat disimpulkan ada pengaruh permainan origami dan playdough terhadap perkembangan anak pada kelompok A di TK Aisyiyah Bustanul Athfal Tahun 2018. Diharapkan kepada orang tua maupun guru untuk lebih meningkatkan frekuensi dalam memberi stimulus permainan terutama permainan origami yang diberikan kepada anak. Kata Kunci : Perkembangan , Anak Prasekolah,  Origami, Playdough ABSTRACTDevelopment is increasing ability or function of all organ systems of the body as a result of increasing maturity or maturity function of the organ system of the body (Dewi, 2013). The purpose of this research is to know the effectiveness difference of origami and playdough on development in preschoolers group A in Aisyiyah Bustanul Athfal Kindergarten in 2018.The research design used is research pre eksperiment with approach pre-test dan post-test. The population studied was all group A children in kindergarten Aisyiyah Bustanul Athfal amounted to 56 children with purposive sampling technique obtained sample 36 respondents. The research instrument used is KPSP sheet. The results were then analyzed by using wilcoxon signed rank.The results of the research show that the development of children before the implementation of giving Origami found half of child development doubt, after the implementation is obtained almost entirely the child's development accordingly. Child development prior to the implementation of Playdough gift obtained most of the development of children doubt, after the implementation is obtained most of the child's development accordingly.  The results of the analysis show that there is an effect of giving origami game and Playdough game to the child development group A in Aisyiyah Bustanul Athfal Kindergarten Year 2018 with the result ρ-value = 0.001 ɑ = 0.05 from the origami group and ρ-value = 0.007 ɑ = 0.05 of the playdough group, while the result of difference analysis that is difference between origami and playdough influence to children development in group A diiyah Aisyiyah Bustanul Athfal Year 2018 with result of ρ-value = 0,043 ɑ = 0,05.Based on the research results can be concluded there is influence of origami and playdough on the development of children in group A in Aisyiyah Bustanul Athfal Kindergarten Year 2018. Expected to parents and teachers to increase the frequency of giving stimulus especially the origami given to the child. Key Words : Development, children preschool, Origami, Playdough

scholarly journals Glucocorticoid Receptor β (GRβ): Beyond Its Dominant-Negative Function

2021 ◽  
Vol 22 (7) ◽  
pp. 3649
Author(s):  
Patricia Ramos-Ramírez ◽  
Omar Tliba
Keyword(s):  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Cell Communication ◽  
Cell Types ◽  
The Body ◽  
Dominant Negative ◽  
Negative Effects ◽  
Independent Manner ◽  
Distinct Cell ◽  
Induced Apoptosis

Glucocorticoids (GCs) act via the GC receptor (GR), a receptor ubiquitously expressed in the body where it drives a broad spectrum of responses within distinct cell types and tissues, which vary in strength and specificity. The variability of GR-mediated cell responses is further extended by the existence of GR isoforms, such as GRα and GRβ, generated through alternative splicing mechanisms. While GRα is the classic receptor responsible for GC actions, GRβ has been implicated in the impairment of GRα-mediated activities. Interestingly, in contrast to the popular belief that GRβ actions are restricted to its dominant-negative effects on GRα-mediated responses, GRβ has been shown to have intrinsic activities and “directly” regulates a plethora of genes related to inflammatory process, cell communication, migration, and malignancy, each in a GRα-independent manner. Furthermore, GRβ has been associated with increased cell migration, growth, and reduced sensitivity to GC-induced apoptosis. We will summarize the current knowledge of GRβ-mediated responses, with a focus on the GRα-independent/intrinsic effects of GRβ and the associated non-canonical signaling pathways. Where appropriate, potential links to airway inflammatory diseases will be highlighted.

scholarly journals Congenital Lumbar Hernia in an 8-Month-Old Boy

2021 ◽  
Vol 15 (1) ◽  
pp. 431-435
Author(s):  
Mohamed Mansy ◽  
Mostafa Kotb ◽  
Mohamed Abouheba
Keyword(s):  
Congenital Anomalies ◽  
Lumbar Hernia ◽  
The Body ◽  
Age Group ◽  
Pediatric Age ◽  
Operative Repair ◽  
Pediatric Age Group ◽  
Organ Systems

Congenital lumbar hernias are uncommonly seen in the pediatric age group, with only about 60 cases reported in the literature. It is usually accompanied by a multitude of congenital anomalies involving different organ systems of the body. For instance, it may involve the ribs, spine, muscles, and the kidneys. Herein, we report a case of congenital lumbar hernia in an 8-month-old boy who underwent an operative repair using a mesh with an uneventful outcome.

scholarly journals Minireview: Thyroid Hormone Transporters: The Knowns and the Unknowns

2011 ◽  
Vol 25 (1) ◽  
pp. 1-14 ◽  
Author(s):  
W. Edward Visser ◽  
Edith C. H. Friesema ◽  
Theo J. Visser
Keyword(s):  
Thyroid Hormone ◽  
Organic Anion ◽  
Psychomotor Retardation ◽  
Cellular Level ◽  
Monocarboxylate Transporter ◽  
Causative Role ◽  
Organic Anion Transporting Polypeptide ◽  
Neurological Abnormalities ◽  
Knockout Animals

The effects of thyroid hormone (TH) on development and metabolism are exerted at the cellular level. Metabolism and action of TH take place intracellularly, which require transport of the hormone across the plasma membrane. This process is mediated by TH transporter proteins. Many TH transporters have been identified at the molecular level, although a few are classified as specific TH transporters, including monocarboxylate transporter (MCT)8, MCT10, and organic anion-transporting polypeptide 1C1. The importance of TH transporters for physiology has been illustrated dramatically by the causative role of MCT8 mutations in males with psychomotor retardation and abnormal serum TH concentrations. Although Mct8 knockout animals have provided insight in the mechanisms underlying parts of the endocrine phenotype, they lack obvious neurological abnormalities. Thus, the pathogenesis of the neurological abnormalities in males with MCT8 mutations is not fully understood. The prospects of identifying other transporters and transporter-based syndromes promise an exciting future in the TH transporter field.

scholarly journals The Act of Controlling Adult Stem Cell Dynamics: Insights from Animal Models

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 667
Author(s):  
Meera Krishnan ◽  
Sahil Kumar ◽  
Luis Johnson Kangale ◽  
Eric Ghigo ◽  
Prasad Abnave
Keyword(s):  
Stem Cells ◽  
Animal Models ◽  
Adult Stem Cells ◽  
The Body ◽  
In Vivo Studies ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Organ Systems

Adult stem cells (ASCs) are the undifferentiated cells that possess self-renewal and differentiation abilities. They are present in all major organ systems of the body and are uniquely reserved there during development for tissue maintenance during homeostasis, injury, and infection. They do so by promptly modulating the dynamics of proliferation, differentiation, survival, and migration. Any imbalance in these processes may result in regeneration failure or developing cancer. Hence, the dynamics of these various behaviors of ASCs need to always be precisely controlled. Several genetic and epigenetic factors have been demonstrated to be involved in tightly regulating the proliferation, differentiation, and self-renewal of ASCs. Understanding these mechanisms is of great importance, given the role of stem cells in regenerative medicine. Investigations on various animal models have played a significant part in enriching our knowledge and giving In Vivo in-sight into such ASCs regulatory mechanisms. In this review, we have discussed the recent In Vivo studies demonstrating the role of various genetic factors in regulating dynamics of different ASCs viz. intestinal stem cells (ISCs), neural stem cells (NSCs), hematopoietic stem cells (HSCs), and epidermal stem cells (Ep-SCs).

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