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Uptake transporters

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https://www.readbyqxmd.com/read/28324217/rare-slc1a1-variants-in-hot-water-epilepsy
#1
Kalpita Rashimi Karan, P Satishchandra, Sanjib Sinha, Anuranjan Anand
Hot water epilepsy is sensory epilepsy, wherein seizures are triggered by an unusual stimulus: contact with hot water. Although genetic factors contribute to the etiology of hot water epilepsy, molecular underpinnings of the disorder remain largely unknown. We aimed to identify the molecular genetic basis of the disorder by studying families with two or more of their members affected with hot water epilepsy. Using a combination of genome-wide linkage mapping and whole exome sequencing, a missense variant was identified in SLC1A1 in a three-generation family...
March 21, 2017: Human Genetics
https://www.readbyqxmd.com/read/28324109/sex-specific-life-course-changes-in-the-neuro-metabolic-phenotype-of-glut3-null-heterozygous-mice-ketogenic-diet-ameliorates-electroencephalographic-seizures-and-improves-sociability
#2
Yun Dai, Yuanzi Zhao, Masatoshi Tomi, Bo-Chul Shin, Shanthie Thamotharan, Andrey Mazarati, Raman Sankar, Elizabeth A Wang, Carlos Cepeda, Michael S Levine, Jingjing Zhang, Andrew Frew, Jeffry R Alger, Peter Clark, Monica Sondhi, Sudatip Kositamongkol, Leah Leibovitch, Sherin U Devaskar
We tested the hypothesis that exposure of glut3+/- mice to a ketogenic diet ameliorates autism-like features which includes aberrant behavior and electrographic seizures. We first investigated the life course sex-specific changes in basal plasma-CSF-brain metabolic profile, brain glucose transport/uptake, glucose and monocarboxylate transporter proteins, and ATP in the presence or absence of systemic insulin administration. Glut3+/- male but not female mice (5m of age) displayed reduced CSF glucose/lactate concentrations with no change in brain Glut1, Mct2, glucose uptake or ATP...
January 24, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324019/no-mediated-regulation-of-glut-by-t3-and-fsh-in-rat-granulosa-cells
#3
Ye Tian, Yu Ding, Juan Liu, Dai Heng, Kaili Xu, Wenbo Liu, Cheng Zhang
Thyroid hormones (THs) are important for normal reproductive function. Although 3,5,3'-triiodothyronine (T3) enhances follicle-stimulating hormone (FSH)-induced preantral follicle growth and granulosa cells development in vitro, little is known about the molecular mechanisms regulating ovarian development via glucose. In this study, we investigated whether and how T3 combines with FSH to regulate glucose transporter protein (GLUT) expression and glucose uptake in granulosa cells. Here, we present evidence that T3 and FSH co-treatment significantly increased GLUT-1/GLUT-4 expression, and translocation in cells, as well as glucose uptake...
March 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323592/measuring-uptake-and-elimination-of-nitrogen-in-humans-at-different-ambient-pressures
#4
Patrik Sundblad, Oskar Frånberg, Christoph Siebenmann, Mikael Gennser
BACKGROUND: To measure nitrogen (N2) wash-out and uptake requires elaborate set-ups, especially when doing the measurements at increased or decreased ambient pressure. Here we present a transportable device for quantifying N2 turnover in humans which can be used at different ambient pressures. METHODS: A modified close-circuit electronic rebreather was used to assess N2 turnover. Changes in N2 volume within the rebreathing circuit, reflecting N2 uptake or washout, were derived from the continuously monitored total system volume and the calculated volumes of oxygen and water vapor...
December 1, 2016: Aerospace Medicine and Human Performance
https://www.readbyqxmd.com/read/28320195/combined-use-of-dopamine-transporter-imaging-dat-spect-and-123-i-metaiodobenzylguanidine-mibg-myocardial-scintigraphy-for-diagnosing-parkinson-s-disease
#5
Fumihito Yoshii, Masafuchi Ryo, Yasuhiko Baba, Takashi Koide, Jun Hashimoto
BACKGROUND: To examine whether combined use of (123)I-FP-CIT dopamine transporter single photon emission computed tomography (DAT-SPECT) and (123)I-MIBG myocardial scintigraphy (MIBG) is superior to either modality alone for diagnosing Parkinson's disease (PD). METHODS: Patients with probable PD (n=120) who underwent both DAT-SPECT and MIBG myocardial scintigraphy within short intervals were enrolled. Specific binding ratio (SBR) of DAT-SPECT images and heart-to-mediastinum (H/M) ratio of MIBG images were used as quantitative measures...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28319392/scaffold-repurposing-of-nucleosides-adenosine-receptor-agonists-enhanced-activity-at-the-human-dopamine-and-norepinephrine-sodium-symporters
#6
Dilip K Tosh, Aaron Janowsky, Amy J Eshleman, Eugene Warnick, Zhan-Guo Gao, Zhoumou Chen, Elizabeth Gizewski, John A Auchampach, Daniela Salvemini, Kenneth A Jacobson
We have repurposed (N)-methanocarba adenosine derivatives (A3 adenosine receptor (AR) agonists) to enhance radioligand binding allosterically at the human dopamine (DA) transporter (DAT) and inhibit DA uptake. We extended the structure-activity relationship of this series with small N(6)-alkyl substitution, 5'-esters, deaza modifications of adenine, and ribose restored in place of methanocarba. C2-(5-Halothien-2-yl)-ethynyl 5'-methyl 9 (MRS7292) and 5'-ethyl 10 (MRS7232) esters enhanced binding at DAT (EC50 ∼ 35 nM) and at the norepinephrine transporter (NET)...
March 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28319329/extracellular-acidosis-and-very-low-na-inhibit-nbcn1-and-nhe1-mediated-net-acid-extrusion-from-mouse-vascular-smooth-muscle-cells
#7
Lisbeth Bonde, Ebbe Boedtkjer
AIM: The electroneutral Na(+) ,HCO3(-) -cotransporter NBCn1 and Na(+) /H(+) -exchanger NHE1 regulate acid-base balance in vascular smooth muscle cells (VSMCs) and modify artery function and structure. Pathological conditions-notably ischemia-can dramatically perturb intracellular (i) and extracellular (o) pH and [Na(+) ]. We examined effects of low [Na(+) ]o and pHo on NBCn1 and NHE1 activity in VSMCs of small arteries. METHODS: We measured pHi by 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein-based fluorescence microscopy of mouse mesenteric arteries and induced intracellular acidification by NH4(+) -prepulse technique...
March 20, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28319056/shoot-to-root-mobile-polypeptides-involved-in-systemic-regulation-of-nitrogen-acquisition
#8
Yuri Ohkubo, Mina Tanaka, Ryo Tabata, Mari Ogawa-Ohnishi, Yoshikatsu Matsubayashi
Plants uptake nitrogen (N) from the soil mainly in the form of nitrate. However, nitrate is often distributed heterogeneously in natural soil. Plants, therefore, have a systemic long-distance signalling mechanism by which N starvation on one side of the root leads to a compensatory N uptake on the other N-rich side(1,2). This systemic N acquisition response is triggered by a root-to-shoot mobile peptide hormone, C-TERMINALLY ENCODED PEPTIDE (CEP), originating from the N-starved roots(3,4), but the molecular nature of the descending shoot-to-root signal remains elusive...
March 20, 2017: Nature Plants
https://www.readbyqxmd.com/read/28318878/insulin-stimulates-transport-of-organic-anion-compounds-mediated-by-organic-anion-transporting-polypeptide-2b1-in-the-human-intestinal-cell-line-caco-2
#9
Taku Kobayashi, Takahiro Koizumi, Masaki Kobayashi, Jiro Ogura, Yuichi Horiuchi, Yuki Kimura, Ayuko Kondo, Ayako Furugen, Katsuya Narumi, Natsuko Takahashi, Ken Iseki
Organic anion transporting polypeptide 2B1 (OATP2B1) is the major uptake transporter in the intestine, and transports various clinically used therapeutic agents. Insulin acts through the insulin receptor in targeted cells, and Rab8A is one of the insulin signaling pathways. The small intestine in humans also expresses insulin receptor and Rab8A. It has been reported that insulin stimulates peptide transporter 1 (PEPT1) expression at the apical membrane and increases uptake of PEPT1 substrates in small intestine epithelial model cells (Caco-2 cells)...
December 27, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28318534/a-multidrug-and-toxic-compound-extrusion-transporter-mediates-berberine-accumulation-into-vacuoles-in-coptis-japonica
#10
Kojiro Takanashi, Yasuyuki Yamada, Takayuki Sasaki, Yoko Yamamoto, Fumihiko Sato, Kazufumi Yazaki
Plants produce a large variety of alkaloids, which have diverse chemical structures and biological activities. Many of these alkaloids accumulate in vacuoles. Although some membrane proteins on tonoplasts have been identified as alkaloid uptake transporters, few have been characterized to date, and relatively little is known about the mechanisms underlying alkaloid transport and accumulation in plant cells. Berberine is a model alkaloid. Although all genes involved in berberine biosynthesis, as well as the master regulator, have been identified, the gene responsible for the final accumulation of berberine at tonoplasts has not been determined...
March 16, 2017: Phytochemistry
https://www.readbyqxmd.com/read/28317852/a-novel-biocontainment-strategy-makes-bacterial-growth-and-survival-dependent-on-phosphite
#11
Ryuichi Hirota, Kenji Abe, Zen-Ichiro Katsuura, Reiji Noguchi, Shigeaki Moribe, Kei Motomura, Takenori Ishida, Maxym Alexandrov, Hisakage Funabashi, Takeshi Ikeda, Akio Kuroda
There is a growing demand to develop biocontainment strategies that prevent unintended proliferation of genetically modified organisms in the open environment. We found that the hypophosphite (H3PO2, HPt) transporter HtxBCDE from Pseudomonas stutzeri WM88 was also capable of transporting phosphite (H3PO3, Pt) but not phosphate (H3PO4, Pi), suggesting the potential for engineering a Pt/HPt-dependent bacterial strain as a biocontainment strategy. We disrupted all Pi and organic Pi transporters in an Escherichia coli strain expressing HtxABCDE and a Pt dehydrogenase, leaving Pt/HPt uptake and oxidation as the only means to obtain Pi...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317731/encapsulation-of-sesamol-in-phosphatidyl-choline-micelles-enhanced-bioavailability-and-anti-inflammatory-activity
#12
P S Yashaswini, Nawneet K Kurrey, Sridevi A Singh
Sesamol, the phenolic degradation product of sesamolin, although recognised for its anti-inflammatory effects, has low bioavailability. In this manuscript, we attempted to improve its bioavailability by encapsulation in mixed phosphatidylcholine micelles. Sesamol could be solubilised and entrapped in phosphatidylcholine mixed micelles (PCS) with 96.8% efficiency (particle size 3.0±0.06nm). Fluorescence spectra of PCS revealed lower relative fluorescence intensity (RFI 112) compared to 'free' sesamol (FS) (RFI 271)...
August 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28316240/heme-gazing-illuminating-eukaryotic-heme-trafficking-dynamics-and-signaling-with-fluorescent-heme-sensors
#13
David A Hanna, Osiris Martinez-Guzman, Amit Ram Reddi
Heme (iron protoporphyrin IX) is an essential protein prosthetic group and signaling molecule required for most life on Earth. All heme dependent processes require the dynamic and rapid mobilization of heme from sites of synthesis or uptake to hemoproteins present in virtually every subcellular compartment. The cytotoxicity and hydrophobicity of heme necessitates that heme mobilization is carefully controlled to mitigate the deleterious effects of this essential toxin. Indeed, a number of disorders, including certain cancers, cardiovascular diseases, and aging and age-related neurodegenerative diseases, are tied to defects in heme homeostasis...
March 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28315682/n-terminal-domain-of-the-cholesterol-transporter-niemann-pick-c1-like-1-npc1l1-is-essential-for-%C3%AE-tocopherol-transport
#14
Jun Kamishikiryo, Misaki Haraguchi, Shunsuke Nakashima, Yuka Tasaka, Hiroe Narahara, Narumi Sugihara, Tetsuya Nakamura, Tetsuo Morita
Both cholesterol and α-tocopherol are essential lipophilic nutrients for humans and animals. Although cholesterol in excess causes severe problems such as coronary heart disease, it is a necessary component of cell membranes and is the precursor for the biosynthesis of steroid hormones and bile acids. Niemann-Pick C1-like 1 (NPC1L1) is a cholesterol transporter that is highly expressed in the small intestine and liver in humans and plays an important role in cholesterol homeostasis. Cholesterol promotes NPC1L1 endocytosis, which is an early step in cholesterol uptake...
March 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28315445/evaluation-of-pept1-transport-of-food-derived-antihypertensive-peptides-ile-pro-pro-and-leu-lys-pro-using-in-vitro-ex-vivo-and-in-vivo-transport-models
#15
John P Gleeson, David J Brayden, Sinéad M Ryan
Ile-Pro-Pro (IPP) and Leu-Lys-Pro (LKP) are food-derived antihypertensive peptides which inhibit angiotensin-converting enzyme (ACE) and may have potential to attenuate hypertension. There is debate over their mechanism of uptake across small intestinal epithelia, but paracellular and PepT1 carrier-mediated uptake are thought to be important routes. The aim of this study was to determine their routes of intestinal permeability using in vitro, ex vivo and in vivo intestinal models. The presence of an apical side pH of 6...
March 14, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28314987/cooperative-inhibitory-effects-of-uremic-toxins-and-other-serum-components-on-oatp1b1-mediated-transport-of-sn-38
#16
Yurie Katsube, Masayuki Tsujimoto, Hiroyoshi Koide, Megumi Ochiai, Ayako Hojyo, Kaori Ogawa, Kengo Kambara, Nao Torii, Daisuke Shima, Taku Furukubo, Satoshi Izumi, Tomoyuki Yamakawa, Tetsuya Minegaki, Kohshi Nishiguchi
PURPOSE: Half-life of SN-38, an active metabolite of irinotecan, remarkably increases in patients with end-stage kidney disease (ESKD), even though SN-38 is excreted in bile. Uremic toxins (UTs), which accumulate in the serum of ESKD patients, were reported to inhibit organic anion-transporting polypeptide (OATP) 1B1-mediated uptake of SN-38; however, the relevance of this finding in a clinical setting is unknown. This study focused on cooperative effects of serum components and UTs on OATP1B1-mediated transport of SN-38...
March 17, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28314825/increased-plasma-exposures-of-conjugated-metabolites-of-morinidazole-in-renal-failure-patients-a-critical-role-of-uremic-toxins
#17
Fandi Kong, Xiaoyan Pang, Kan Zhong, Zitao Guo, Xiuli Li, Dafang Zhong, Xiaoyan Chen
Morinidazole is a 5-nitroimidazole drug. Its sulfate conjugate M7 was a sensitive substrate of organic anion transporter 1 (OAT1) and OAT3, whereas N+-glucuronides M8-1 and M8-2 were only OAT3 substrates. In chronic renal failure (CRF) patients, plasma exposures of the three conjugates increased by 15-fold, which were also found in 5/6 nephrectomized (5/6 Nx) rats in this study. Although the transcriptions of Oat1 and Oat3 in 5/6 Nx rat kidneys decreased by 50%, no difference was observed on the three conjugate uptakes between control and 5/6 Nx rat kidney slices...
March 17, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28314816/characterization-of-a-human-point-mutation-of-vglut3-p-a211v-in-the-rodent-brain-suggests-a-non-uniform-distribution-of-the-transporter-in-synaptic-vesicles
#18
Lauriane Ramet, Johannes Zimmermann, Tiphaine Bersot, Odile Poirel, Stéphanie De Gois, Katlin Silm, Diana Yae Sakae, Nina Mansouri-Guilani, Marie-Josée Bourque, Louis-Eric Trudeau, Nicolas Pietrancosta, Stéphanie Daumas, Véronique Bernard, Christian Rosenmund, Salah El Mestikawy
The atypical vesicular glutamate transporter type 3 (VGLUT3) is expressed by sub-populations of neurons using acetylcholine, GABA or serotonin as neurotransmitters. In addition, VGLUT3 is expressed in the inner hair cells of the auditory system. A mutation (p.A211V) in the gene that encodes VGLUT3 is responsible for progressive deafness in two unrelated families. In this study, we investigated the consequences of the p.A211V mutation in cell cultures and in the central nervous system (CNS) of a mutant mouse...
March 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28304381/tnf-%C3%AE-stimulates-endothelial-palmitic-acid-transcytosis-and-promotes-insulin-resistance
#19
Wenjing Li, Xiaoyan Yang, Tao Zheng, Shasha Xing, Yaogong Wu, Fang Bian, Guangjie Wu, Ye Li, Juyi Li, Xiangli Bai, Dan Wu, Xiong Jia, Ling Wang, Lin Zhu, Si Jin
Persistent elevation of plasma TNF-α is a marker of low grade systemic inflammation. Palmitic acid (PA) is the most abundant type of saturated fatty acid in human body. PA is bound with albumin in plasma and could not pass through endothelial barrier freely. Albumin-bound PA has to be transported across monolayer endothelial cells through intracellular transcytosis, but not intercellular diffusion. In the present study, we discovered that TNF-α might stimulate PA transcytosis across cardiac microvascular endothelial cells, which further impaired the insulin-stimulated glucose uptake by cardiomyocytes and promoted insulin resistance...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303916/copper-transporters-are-responsible-for-copper-isotopic-fractionation-in-eukaryotic-cells
#20
Jean-Loup Cadiou, Sylvain Pichat, Victor P Bondanese, Alexandre Soulard, Toshiyuki Fujii, Francis Albarède, Philippe Oger
Copper isotopic composition is altered in cancerous compared to healthy tissues. However, the rationale for this difference is yet unknown. As a model of Cu isotopic fractionation, we monitored Cu uptake in Saccharomyces cerevisiae, whose Cu import is similar to human. Wild type cells are enriched in (63)Cu relative to (65)Cu. Likewise, (63)Cu isotope enrichment in cells without high-affinity Cu transporters is of slightly lower magnitude. In cells with compromised Cu reductase activity, however, no isotope fractionation is observed and when Cu is provided solely in reduced form for this strain, copper is enriched in (63)Cu like in the case of the wild type...
March 17, 2017: Scientific Reports
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