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https://www.readbyqxmd.com/read/28645914/bile-salt-homeostasis-in-normal-and-bsep-gene-knock-out-rats-with-single-and-repeated-doses-of-troglitazone
#1
Yaofeng Cheng, Shenjue Chen, Chris Freeden, Weiqi Chen, Yueping Zhang, Pamela Abraham, David Nelson, William G Humphreys, Jinpin Gan, Yurong Lai
The interference of bile acid secretion through bile salt export pump (BSEP) inhibition was one of the mechanisms for troglitazone (TGZ) induced hepatotoxicity. Here we investigated the impact of single or repeated oral doses of TGZ (200 mg/kg/day, 7 days) on bile acid homoeostasis in wild-type (WT) and Bsep KO rats. Following oral doses, plasma exposures of TGZ were not different between WT and KO rats, and were similar on Day-1 and Day-7. However, plasma exposures of the major metabolite, troglitazone sulfate (TS), in KO rats were 7...
June 23, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28636910/prp40-homolog-a-is-a-novel-centrin-target
#2
Adalberto Díaz Casas, Walter J Chazin, Belinda Pastrana-Ríos
Pre-mRNA processing protein 40 (Prp40) is a nuclear protein that has a role in pre-mRNA splicing. Prp40 possesses two leucine-rich nuclear export signals, but little is known about the function of Prp40 in the export process. Another protein that has a role in protein export is centrin, a member of the EF-hand superfamily of Ca(2+)-binding proteins. Prp40 was found to be a centrin target by yeast-two-hybrid screening using both Homo sapiens centrin 2 (Hscen2) and Chlamydomonas reinhardtii centrin (Crcen). We identified a centrin-binding site within H...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28633435/mcm3ap-in-recessive-charcot-marie-tooth-neuropathy-and-mild-intellectual-disability
#3
Emil Ylikallio, Rosa Woldegebriel, Manuela Tumiati, Pirjo Isohanni, Monique M Ryan, Zornitza Stark, Maie Walsh, Sarah L Sawyer, Katrina M Bell, Alicia Oshlack, Paul J Lockhart, Mariia Shcherbii, Alejandro Estrada-Cuzcano, Derek Atkinson, Taila Hartley, Martine Tetreault, Inge Cuppen, W Ludo van der Pol, Ayse Candayan, Esra Battaloglu, Yesim Parman, Koen L I van Gassen, Marie-José H van den Boogaard, Kym M Boycott, Liisa Kauppi, Albena Jordanova, Tuula Lönnqvist, Henna Tyynismaa
Defects in mRNA export from the nucleus have been linked to various neurodegenerative disorders. We report mutations in the gene MCM3AP, encoding the germinal center associated nuclear protein (GANP), in nine affected individuals from five unrelated families. The variants were associated with severe childhood onset primarily axonal (four families) or demyelinating (one family) Charcot-Marie-Tooth neuropathy. Mild to moderate intellectual disability was present in seven of nine affected individuals. The affected individuals were either compound heterozygous or homozygous for different MCM3AP variants, which were predicted to cause depletion of GANP or affect conserved amino acids with likely importance for its function...
June 19, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28631420/expression-of-pten-long-mediated-by-crispr-cas9-can-repress-u87-cell-proliferation
#4
Na Fang, Tingxuan Gu, Yahui Wang, Shuzhen Wang, Fengling Wang, Yang An, Wenqiang Wei, Weijuan Zhang, Xiangqian Guo, Adil J Nazarali, Shaoping Ji
PTEN is a tumour suppressor that is frequently mutated in a variety of cancers. Hence, PTEN has significant potential as a therapeutic molecule. PTEN-long is an alternative translation variant, with an additional 173 amino acids added to the N-terminal of the canonical PTEN when CUG of the mRNA is utilized as the start codon. PTEN-long is secreted into serum and can re-enter cells throughout the body. One of the major barriers for gene therapy is to efficiently and specifically deliver DNA or RNA material to target cells...
June 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28627642/effect-of-retinoid-x-receptor-%C3%AE-nuclear-export-inhibition-on-apoptosis-of-neurons-in%C3%A2-vivo-and-in%C3%A2-vitro
#5
Yingchun Liu, Jiangguo Tang, Xiaoxiao Gao, Min Wang, Jie Shen, Xiaoqing You
Alzheimer's disease (AD), which is characte-rized by excessive apoptosis of neurons, is considered to be a global public health crisis. Retinoid-induced apoptosis is dependent on the orphan nuclear receptor Nur77, a transcription factor that is expressed predominantly in brain tissues. Nur77 nuclear export requires retinoid X receptor‑α (RXRα) as a carrier. However, the involvement of Nur77 in mediating β‑amyloid (Aβ)‑induced neuronal apoptosis has not yet been elucidated. The primary aim of the present study was to investigate the potential of Nur77 in Aβ‑induced neuron apoptosis, and to evaluate the effect of RXRα nuclear export inhibition on neuronal apoptosis...
June 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28592444/cellular-differentiation-state-modulates-the-mrna-export-activity-of-sr-proteins
#6
Valentina Botti, François McNicoll, Michaela C Steiner, Florian M Richter, Anfisa Solovyeva, Marius Wegener, Oliver D Schwich, Ina Poser, Kathi Zarnack, Ilka Wittig, Karla M Neugebauer, Michaela Müller-McNicoll
SR proteins function in nuclear pre-mRNA processing, mRNA export, and translation. To investigate their cellular dynamics, we developed a quantitative assay, which detects differences in nucleocytoplasmic shuttling among seven canonical SR protein family members. As expected, SRSF2 and SRSF5 shuttle poorly in HeLa cells but surprisingly display considerable shuttling in pluripotent murine P19 cells. Combining individual-resolution cross-linking and immunoprecipitation (iCLIP) and mass spectrometry, we show that elevated arginine methylation of SRSF5 and lower phosphorylation levels of cobound SRSF2 enhance shuttling of SRSF5 in P19 cells by modulating protein-protein and protein-RNA interactions...
June 7, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28591710/selective-inhibitors-of-nuclear-export-sine-compounds-block-proliferation-and-migration-of-triple-negative-breast-cancer-cells-by-restoring-expression-of-arrdc3
#7
Young Hwa Soung, Trinayan Kashyap, Thalia Nguyen, Garima Yadav, Hua Chang, Yosef Landesman, Jun Chung
Arrestin-related domain-containing protein-3 (ARRDC3) is one of 6 mammalian arrestins, which suppresses metastasis by inducing degradation of phosphorylated β2-adrenergic receptor (β2 AR) and integrin β4 (ITG β4). Our previous studies demonstrated that expression of ARRDC3 is epigentically silenced in Triple Negative Breast Cancer (TNBC) cells, and the forced expression of ARRDC3 significantly reduced the invasive potential of TNBC cells. In the current study, we found that Selective Inhibitors of Nuclear Export (SINE) compounds (KPT-185 and selinexor (KPT-330)) restore ARRDC3 expression in TNBC cell lines (MDA-MB-231 and MDA-MB-468) at both the mRNA and protein level in a dose and time course dependent manner...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28588505/multiple-calcium-export-exchangers-and-pumps-are-a-prominent-feature-of-enamel-organ-cells
#8
Sarah Y T Robertson, Xin Wen, Kaifeng Yin, Junjun Chen, Charles E Smith, Michael L Paine
Calcium export is a key function for the enamel organ during all stages of amelogenesis. Expression of a number of ATPase calcium transporting, plasma membrane genes (ATP2B1-4/PMCA1-4), solute carrier SLC8A genes (sodium/calcium exchanger or NCX1-3), and SLC24A gene family members (sodium/potassium/calcium exchanger or NCKX1-6) have been investigated in the developing enamel organ in earlier studies. This paper reviews the calcium export pathways that have been described and adds novel insights to the spatiotemporal expression patterns of PMCA1, PMCA4, and NCKX3 during amelogenesis...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28582681/translational-control-and-the-cancer-cell-response-to-stress
#9
REVIEW
Nathaniel Robichaud, Nahum Sonenberg
The evidence for the importance of aberrant translation in cancer cells is overwhelming. Reflecting the wealth of data, there are excellent reviews delineating how ribosomes and initiation factors are linked to cancer [1-3], and the therapeutic strategies being devised to target them [4]. Changes in translational efficiency can engender a malignant phenotype without the need for chromatin reorganization, transcription, splicing and mRNA export [5,6]. Thus, cancer-related modulations of the translational machinery are ideally suited to allow cancer cells to respond to the various stresses encountered along the path of tumorigenesis and organism-wide dissemination [7(•),8,9,10(•)]...
June 2, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28577934/assessing-mrna-nuclear-export-in-mammalian-cells-by-microinjection
#10
Eliza S Lee, Alexander F Palazzo
The nuclear export of mRNAs is an important yet little understood part of eukaryotic gene expression. One of the easiest methods for monitoring mRNA export in mammalian tissue culture cells is through the microinjection of DNA plasmids into the nucleus and monitoring the distribution of the transcribed product over time. Here we describe how to setup a microscope equipped with a micromanipulator used in cell microinjections, and we explain how to perform a nuclear mRNA export assay and obtain the nuclear export rate for any given mRNA...
May 31, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28557706/downregulation-of-p68-rna-helicase-ddx5-activates-a-survival-pathway-involving-mtor-and-mdm2-signals
#11
M Kokolo, M Bach-Elias
The DEAD box p68 RNA helicase (DDX5) is required to manipulate RNA structures implicated in mRNA/rRNA processing and transcript export, and acts as a co-activator for a range of transcription factors. Previous research has indicated that p68 RNA helicase may also be important in tumour development. Wild-type HeLa and stable HeLa (clone 13) cell cultures containing RNAi-mediated depletion of p68 RNA helicase induced by doxycycline (DOX) were used to study how the p68 RNA helicase affects the mTOR cell signalling pathway...
2017: Folia Biologica (Praha)
https://www.readbyqxmd.com/read/28554770/the-actin-binding-cytoskeletal-protein-moesin-is-involved-in-nuclear-mrna-export
#12
Ildikó Kristó, Csaba Bajusz, Barbara N Borsos, Tibor Pankotai, Joseph Dopie, Ferenc Jankovics, Maria K Vartiainen, Miklós Erdélyi, Péter Vilmos
Current models imply that the evolutionarily conserved, actin-binding Ezrin-Radixin-Moesin (ERM) proteins perform their activities at the plasma membrane by anchoring membrane proteins to the cortical actin network. Here we show that beside its cytoplasmic functions, the single ERM protein of Drosophila, Moesin, has a novel role in the nucleus. The activation of transcription by heat shock or hormonal treatment increases the amount of nuclear Moesin, indicating biological function for the protein in the nucleus...
May 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28550085/knockdown-of-sodium-calcium-exchanger-1-induces-epithelial-to-mesenchymal-transition-in-kidney-epithelial-cells
#13
Sona Lakshme Balasubramaniam, Anilkumar Gopalakrishnapillai, Nicholas J Petrelli, Sonali P Barwe
Mesenchymal to epithelial transition (MET) and epithelial to mesenchymal transition (EMT) are important processes in kidney development. Failure to undergo MET during development leads to the initiation of Wilms tumor (WT) whereas EMT contributes to the development of renal cell carcinomas (RCC). The role of calcium regulators in governing these processes is becoming evident. We demonstrated earlier that Na+/Ca2+ exchanger 1 (NCX1), a major calcium exporter in renal epithelial cells, regulates epithelial cell motility...
May 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28549616/pectin-penta-oligogalacturonide-reduces-cholesterol-accumulation-by-promoting-bile-acid-biosynthesis-and-excretion-in-high-cholesterol-fed-mice
#14
Ru-Gang Zhu, Yan-Di Sun, Yu-Ting Hou, Jun-Gang Fan, Gang Chen, Tuo-Ping Li
Haw pectin penta-oligogalacturonide (HPPS) has important role in improving cholesterol metabolism and promoting the conversion of cholesterol to bile acids (BA) in mice fed high-cholesterol diet (HCD). However, the mechanism is not clear. This study aims to investigate the effects of HPPS on cholesterol accumulation and the regulation of hepatic BA synthesis and transport in HCD-fed mice. Results showed that HPPS significantly decreased plasma and hepatic TC levels but increased plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) levels, compared to HCD...
June 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28549066/alternative-exon-definition-events-control-the-choice-between-nuclear-retention-and-cytoplasmic-export-of-u11-u12-65k-mrna
#15
Jens Verbeeren, Bhupendra Verma, Elina H Niemelä, Karen Yap, Eugene V Makeyev, Mikko J Frilander
Cellular homeostasis of the minor spliceosome is regulated by a negative feed-back loop that targets U11-48K and U11/U12-65K mRNAs encoding essential components of the U12-type intron-specific U11/U12 di-snRNP. This involves interaction of the U11 snRNP with an evolutionarily conserved splicing enhancer giving rise to unproductive mRNA isoforms. In the case of U11/U12-65K, this mechanism controls the length of the 3' untranslated region (3'UTR). We show that this process is dynamically regulated in developing neurons and some other cell types, and involves a binary switch between translation-competent mRNAs with a short 3'UTR to non-productive isoforms with a long 3'UTR that are retained in the nucleus or/and spliced to the downstream amylase locus...
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28545058/a-systematic-genomic-screen-implicates-nucleocytoplasmic-transport-and-membrane-growth-in-nuclear-size-control
#16
Kazunori Kume, Helena Cantwell, Frank R Neumann, Andrew W Jones, Ambrosius P Snijders, Paul Nurse
How cells control the overall size and growth of membrane-bound organelles is an important unanswered question of cell biology. Fission yeast cells maintain a nuclear size proportional to cellular size, resulting in a constant ratio between nuclear and cellular volumes (N/C ratio). We have conducted a genome-wide visual screen of a fission yeast gene deletion collection for viable mutants altered in their N/C ratio, and have found that defects in both nucleocytoplasmic mRNA transport and lipid synthesis alter the N/C ratio...
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28534483/5-methylcytosine-mediates-nuclear-export-of-mrna
#17
Dan Dominissini, Gideon Rechavi
5-methylcytosine was shown before to be an epitranscriptomic mark. Yang et al. now explored the unique topology of this mRNA modification, identified its writer and demonstrated its involvement in nuclear-cytoplasmic shuttling mediated by a specific reader.
June 2017: Cell Research
https://www.readbyqxmd.com/read/28516119/affinity-pulldown-of-biotinylated-rna-for-detection-of-protein-rna-complexes
#18
Amaresh C Panda, Jennifer L Martindale, Myriam Gorospe
RNA-binding proteins (RBPs) have recently emerged as crucial players in the regulation of gene expression. The interactions of RBPs with target mRNAs control the levels of gene products by altering different regulatory steps, including pre-mRNA splicing and maturation, nuclear mRNA export, and mRNA stability and translation (Glisovic et al., 2008). There are several methodologies available today to identify RNAs bound to specific RBPs; some detect only recombinant molecules in vitro, others detect recombinant and endogenous molecules, while others detect only endogenous molecules...
December 20, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28515301/the-influenza-a-virus-ns1-protein-promotes-efficient-nuclear-export-of-unspliced-viral-m1-mrna
#19
Carina F Pereira, Eliot K C Read, Helen M Wise, Maria J Amorim, Paul Digard
Influenza A virus mRNAs are transcribed by the viral RNA-dependent RNA polymerase in the cell nucleus before being exported to the cytoplasm for translation. Segment 7 produces two major transcripts: an unspliced mRNA that encodes the M1 matrix protein and a spliced transcript that encodes the M2 ion channel. Export of both mRNAs is dependent on the cellular NXF1/TAP pathway but it is unclear how they are recruited to the export machinery or how the intron-containing but unspliced M1 mRNA bypasses the normal quality control checkpoints...
May 17, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28507548/iron-and-hepcidin-independent-downregulation-of-the-iron-exporter-ferroportin-in-macrophages-during-salmonella-infection
#20
Alexandra Willemetz, Sean Beatty, Etienne Richer, Aude Rubio, Anne Auriac, Ruth J Milkereit, Olivier Thibaudeau, Sophie Vaulont, Danielle Malo, François Canonne-Hergaux
Retention of iron in tissue macrophages via upregulation of hepcidin (HAMP) and downregulation of the iron exporter ferroportin (FPN) is thought to participate in the establishment of anemia of inflammation after infection. However, an upregulation of FPN has been proposed to limit macrophages iron access to intracellular pathogens. Therefore, we studied the iron homeostasis and in particular the regulation of FPN after infection with Salmonella enterica serovar Typhimurium in mice presenting tissue macrophages with high iron (AcB61), basal iron (A/J and wild-type mice), or low iron (Hamp knock out, Hamp(-/-)) levels...
2017: Frontiers in Immunology
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