scholarly journals Decreased Equilibrative Nucleoside Transporter 1 (ENT1) Activity Contributes to the High Extracellular Adenosine Levels in Mesenchymal Glioblastoma Stem-Like Cells

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1914 ◽  
Author(s):  
Sebastián Alarcón ◽  
María de los Ángeles Toro ◽  
Carolina Villarreal ◽  
Rómulo Melo ◽  
Rodrigo Fernández ◽  
...  
Keyword(s):  
Adenosine Monophosphate ◽  
Prostatic Acid Phosphatase ◽  
Cell Subpopulation ◽  
Migration And Invasion ◽  
Nucleoside Transporter ◽  
Extracellular Adenosine ◽  
Adenosine Uptake ◽  
A Cell ◽  
High Level ◽  
Lower Expression

Glioblastoma multiforme is one of the most malignant types of cancer. This is mainly due to a cell subpopulation with an extremely aggressive potential, called glioblastoma stem-like cells (GSCs). These cells produce high levels of extracellular adenosine which has been associated with increased chemoresistance, migration, and invasion in glioblastoma. In this study, we attempted to elucidate the mechanisms that control extracellular adenosine levels in GSC subtypes. By using primary and U87MG-derived GSCs, we associated increased extracellular adenosine with the mesenchymal phenotype. [3H]-adenosine uptake occurred mainly through the equilibrative nucleoside transporters (ENTs) in GSCs, but mesenchymal GSCs have lower expression and ENT1-mediated uptake activity than proneural GSCs. By analyzing expression and enzymatic activity, we determined that ecto-5′-nucleotidase (CD73) is predominantly expressed in proneural GSCs, driving AMPase activity. While in mesenchymal GSCs, both CD73 and Prostatic Acid Phosphatase (PAP) contribute to the AMP (adenosine monophosphate) hydrolysis. We did not observe significant differences between the expression of proteins involved in the metabolization of adenosine among the GCSs subtypes. In conclusion, the lower expression and activity of the ENT1 transporter in mesenchymal GSCs contributes to the high level of extracellular adenosine that these GSCs present.

scholarly journals Adenosine Depletion as A New Strategy to Decrease Glioblastoma Stem-Like Cells Aggressiveness

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1353 ◽  
Author(s):  
Ignacio Niechi ◽  
Atenea Uribe-Ojeda ◽  
José Ignacio Erices ◽  
Ángelo Torres ◽  
Daniel Uribe ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Cell Subpopulation ◽  
Migration And Invasion ◽  
Transwell Assay ◽  
Extracellular Adenosine ◽  
Hypoxic Conditions ◽  
New Strategy ◽  
Dependent Cell ◽  
A Cell ◽  
The Brain

Glioblastoma is the brain tumor with the worst prognosis. This is mainly due to a cell subpopulation with an extremely aggressive potential, called glioblastoma stem-like cells (GSCs). These cells produce high levels of extracellular adenosine, which are increased even more under hypoxic conditions. Under hypoxia, adenosine signaling is related to HIF-2α expression, enhancing cell aggressiveness. Adenosine can be degraded using recombinant adenosine deaminase (ADA) to revert its pathological effects. The aim of this study was to degrade adenosine using ADA in order to decrease malignancy of GSCs. Adenosine depletion was performed using recombinant ADA. Migration and invasion were measured by transwell and matrigel-coated transwell assay, respectively. HIF-2α-dependent cell migration/invasion decreased in GSCs treated with ADA under hypoxia. MRPs-mediated chemoresistance and colony formation decreased in treatment with ADA. In conclusion, adenosine depletion using adenosine deaminase decreases GSCs aggressiveness.

Ethanol metabolism and inhibition of nucleoside uptake lead to increased extracellular adenosine in hepatocytes

1992 ◽  
Vol 262 (5) ◽  
pp. C1175-C1180 ◽  
Author(s):  
L. E. Nagy
Keyword(s):  
Cultured Cells ◽  
Primary Cultures ◽  
Rat Hepatocytes ◽  
Ethanol Metabolism ◽  
Nucleoside Transporter ◽  
Extracellular Adenosine ◽  
Mediated Effects ◽  
Adenosine Uptake ◽  
Nucleoside Uptake ◽  
Acute And Chronic Effects

Recent evidence suggests that adenosine mediates many of the acute and chronic effects of ethanol in both cultured cells and whole animals. These adenosine-mediated effects of ethanol result from ethanol-induced increases in extracellular adenosine. Acute exposure of primary cultures of rat hepatocytes to 12.5-200 mM ethanol increased extracellular adenosine concentrations by 20-35%. Pretreatment of hepatocytes with 100 microM 4-methylpyrazole, an inhibitor of alcohol dehydrogenase, completely blocked ethanol-induced increases in extracellular adenosine at 12.5 and 25 mM ethanol. However, even in the presence of 4-methylpyrazole, ethanol at concentrations greater than 50 mM still increased extracellular adenosine concentrations. This increase appears to be due to ethanol inhibition of adenosine uptake via the nucleoside transporter (50% inhibitory concentration, 28 mM). After chronic treatment with 100 mM ethanol for 48 h, acute challenge with ethanol no longer inhibited adenosine uptake, i.e., the nucleoside transporter had become tolerant to ethanol. Moreover, in these chronically treated cells, ethanol-induced increases in extracellular adenosine were completely blocked by treatment with 4-methylpyrazole at all concentrations of ethanol. Taken together, these results suggest that increased extracellular adenosine in hepatocytes is dependent on both ethanol oxidation and inhibition of adenosine uptake via the nucleoside transporter.

scholarly journals Ethanol increases extracellular adenosine by inhibiting adenosine uptake via the nucleoside transporter.

1990 ◽  
Vol 265 (4) ◽  
pp. 1946-1951 ◽  
Author(s):  
L E Nagy ◽  
I Diamond ◽  
D J Casso ◽  
C Franklin ◽  
A S Gordon
Keyword(s):  
Nucleoside Transporter ◽  
Extracellular Adenosine ◽  
Adenosine Uptake

scholarly journals Transcriptome Analysis Provides Insights into the Mechanism of Astaxanthin Enrichment in a Mutant of the Ridgetail White Prawn Exopalaemon carinicauda

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 618
Author(s):  
Yue Jin ◽  
Shihao Li ◽  
Yang Yu ◽  
Chengsong Zhang ◽  
Xiaojun Zhang ◽  
...  
Keyword(s):  
Transcriptome Analysis ◽  
Underlying Mechanism ◽  
Biological Processes ◽  
Wild Type ◽  
Expression Levels ◽  
In The Wild ◽  
Cuticle Proteins ◽  
Apolipoprotein D ◽  
High Level ◽  
Lower Expression

A mutant of the ridgetail white prawn, which exhibited rare orange-red body color with a higher level of free astaxanthin (ASTX) concentration than that in the wild-type prawn, was obtained in our lab. In order to understand the underlying mechanism for the existence of a high level of free astaxanthin, transcriptome analysis was performed to identify the differentially expressed genes (DEGs) between the mutant and wild-type prawns. A total of 78,224 unigenes were obtained, and 1863 were identified as DEGs, in which 902 unigenes showed higher expression levels, while 961 unigenes presented lower expression levels in the mutant in comparison with the wild-type prawns. Based on Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis, as well as further investigation of annotated DEGs, we found that the biological processes related to astaxanthin binding, transport, and metabolism presented significant differences between the mutant and the wild-type prawns. Some genes related to these processes, including crustacyanin, apolipoprotein D (ApoD), cathepsin, and cuticle proteins, were identified as DEGs between the two types of prawns. These data may provide important information for us to understand the molecular mechanism of the existence of a high level of free astaxanthin in the prawn.

The effect of diazepam on adenosine uptake and adenosine-stimuiated adenylate cyclase in guinea-pig brain

1982 ◽  
Vol 60 (3) ◽  
pp. 302-307 ◽  
Author(s):  
M. J. York ◽  
L. P. Davies
Keyword(s):  
Adenylate Cyclase ◽  
Guinea Pig ◽  
Adenosine Deaminase ◽  
Small Component ◽  
Extracellular Adenosine ◽  
Pig Brain ◽  
Adenosine Uptake ◽  
Adenosine Antagonist ◽  
Guinea Pig Brain ◽  
Stimulation Of

We have used the adenosine-stimulated adenylate cyclase of guinea-pig brain to examine the potency of diazepam as an adenosine uptake inhibitor. Diazepam at concentrations in the range 10–500 μM stimulates the production of cAMP in incubated slices of guinea-pig cerebral cortex, with maximal fivefold stimulations over basal levels by 200 μM diazepam. The increases can be largely (but not completely) blocked by the adenosine antagonist theophylline or by addition of excess adenosine deaminase to the system. It appears that the stimulation of cAMP production is due to a blockade of adenosine uptake which results in an increase in extracellular adenosine and concomitant activation of the adenosine receptor coupled to adenylate cyclase. Since the cAMP response to standard adenosine uptake blockers (dipyridamole, dilazep) can be completely blocked by theophylline or adenosine deaminase, a small component of the diazepam response cannot be explained by an adenosine effect. The concentration of diazepam at which the first significant cAMP increase occurs is 10 μM or slightly lower. This is significantly higher than the concentration of diazepam needed to saturate the pharmacologically characterized central nervous system receptors for benzodiazepines.

scholarly journals Order and stochasticity in the folding of individual Drosophila genomes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sergey V. Ulianov ◽  
Vlada V. Zakharova ◽  
Aleksandra A. Galitsyna ◽  
Pavel I. Kos ◽  
Kirill E. Polovnikov ◽  
...  
Keyword(s):  
Random Walk ◽  
High Resolution ◽  
3D Genome ◽  
Topologically Associating Domains ◽  
Chromatin Folding ◽  
A Cell ◽  
Single Nucleus ◽  
High Level ◽  
Cell To Cell Variability

AbstractMammalian and Drosophila genomes are partitioned into topologically associating domains (TADs). Although this partitioning has been reported to be functionally relevant, it is unclear whether TADs represent true physical units located at the same genomic positions in each cell nucleus or emerge as an average of numerous alternative chromatin folding patterns in a cell population. Here, we use a single-nucleus Hi-C technique to construct high-resolution Hi-C maps in individual Drosophila genomes. These maps demonstrate chromatin compartmentalization at the megabase scale and partitioning of the genome into non-hierarchical TADs at the scale of 100 kb, which closely resembles the TAD profile in the bulk in situ Hi-C data. Over 40% of TAD boundaries are conserved between individual nuclei and possess a high level of active epigenetic marks. Polymer simulations demonstrate that chromatin folding is best described by the random walk model within TADs and is most suitably approximated by a crumpled globule build of Gaussian blobs at longer distances. We observe prominent cell-to-cell variability in the long-range contacts between either active genome loci or between Polycomb-bound regions, suggesting an important contribution of stochastic processes to the formation of the Drosophila 3D genome.

Introns excised from immunoglobulin pre-mRNAs exist as discrete species

1984 ◽  
Vol 4 (10) ◽  
pp. 2017-2022
Author(s):  
C Coleclough ◽  
D Wood
Keyword(s):  
Cell Lines ◽  
Resolving Power ◽  
Linear Molecule ◽  
Immunoglobulin Kappa ◽  
Polyadenylic Acid ◽  
Nonionic Detergent ◽  
A Cell ◽  
Active Locus ◽  
B Lineage ◽  
High Level

We have discovered a new class of transcripts of immunoglobulin kappa genes in RNA from B-lineage cells. These transcripts have the properties predicted of free introns excised from kappa mRNA precursors. RNA extracted from populations of normal mouse spleen cells polyclonally activated with B-cell mitogens contains four such transcripts; their electrophoretic mobilities correspond to the distances between the intron-exon boundary of the C kappa region and the four useable J kappa elements, and their relative abundance reflects the relative usage of those J segments. Analysis of RNA from monoclonal kappa-expressing cell lines reveals that one active locus produces one free intron, its size determined by which J element is used in that locus. Apart from their distinctive size, free introns are identified by their lack of polyadenylic acid and their ability to hybridize to cloned probes containing intron sequences, but not to the adjacent V or C exonic sequences. They have a characteristic subcellular distribution, being extractable from nuclei by treatment with nonionic detergent; nuclei thus treated retain most of the primary mRNA precursors, but few of the free introns. A high level of kappa gene expression is not a prerequisite of a cell containing detectable free kappa introns; the lymphoma 38c has only 5% or less of the amount of kappa mRNA that the plasmacytoma MCP-11 contains, yet the ratio of free intron to mRNA precursor is about the same in both cell lines. When analyzed by electrophoretic separation of sufficient resolving power, the free introns due to a single kappa locus resolve into two discrete species. We consider that this most likely reflects the existence of two conformers of the intron, one presumably a covalently intact circle and the other linear molecule.

An Effective Cell Coculture Platform Based on the Electrospun Microtube Array Membrane for Nerve Regeneration

2017 ◽  
Vol 204 (3-4) ◽  
pp. 179-190 ◽  
Author(s):  
V. Chia-Hsuan Tseng ◽  
Chee Ho Chew ◽  
Wan-Ting Huang ◽  
Yang-Kao Wang ◽  
Ko-Shao Chen ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Chain Reaction ◽  
Tissue Culture Polystyrene ◽  
Coculture System ◽  
Submicron Scale ◽  
A Cell ◽  
Polymerase Chain ◽  
Transwell System ◽  
Lower Expression ◽  
Microtube Array

Recently, a novel substrate known as an electrospun polylactic acid (PLLA) microtube array membrane (MTAM) was successfully developed as a cell coculture platform. Structurally, this substrate is made up of one-to-one connected, ultrathin, submicron scale fibers that are arranged in an arrayed formation. Its unique structure confers several key advantages which are beneficial in a cell coculture system. In this study, the interaction between rat fetal neural stem cells (NSC) and astrocytes was examined by comparing the outcome of a typical Transwell-based coculture system and that of an electrospun PLLA MTAM-based coculture system. Compared to tissue culture polystyrene (TCP) and Transwell coculture inserts, a superior cell viability of NSC was observed when cultured in lumens of electrospun PLLA MTAM (with supportive immunostaining images). Reverse transcription polymerase chain reaction revealed a strong interaction between astrocytes and NSC through a higher expression of doublecortin and a lower expression of nestin. These data demonstrate that MTAM is clearly a better coculture platform than the traditional Transwell system.

scholarly journals Podophyllotoxin and Quercetin in Silico Derivatives Docking Analysis with Cyclooxygenase-2 and Aminopeptidase-N

2021 ◽  
Author(s):  
A.E. Manukyan ◽  
A.A. Hovhannisyan
Keyword(s):  
In Silico ◽  
Biological Activities ◽  
Three Dimensional ◽  
Aminopeptidase N ◽  
Docking Analysis ◽  
Quercetin Derivatives ◽  
Pubchem Database ◽  
A Cell ◽  
Cox 2 ◽  
High Level

ABSTRACTThe cyclooxygenase (COX) enzymes are tumor markers, the inhibition of which can be used in the prevention and therapy of carcinogenesis. It was found that COX-2 IS considered as targets for tumor inhibition. Aminopeptidase N (APN) is a type II membrane-bound metalloprotease associated with cancer, being identified as a cell marker on the surface of malignant myeloid cells and reached a high level of expression in progressive tumors. In anticancer therapy, plant compounds are considered that can inhibit their activity. Modeling of the COX-2 and APN enzymes was carried out on the basis of molecular models of three-dimensional structures from the PDB database [PDB ID: 5f19, 4fyq] RCSB. For docking analysis, 3D ligand models were created using MarvinSketch based on the PubChem database [CID: 5280343, 5281654]. In silico experiments, for the first time, revealed the possible interaction and inhibition of COX-2 and APN by quercetin and quercetin derivatives. Aspirin and Marimastat were taken to compare the results. Possible biological activities and possible side effects of the ligands have been identified.

Knowledge Disclosed in Patent Documents as Source of Information to Address Emergencies: A Strategy to Achieve Technological Developments Addressing COVID-19

2021 ◽  
Vol 15 ◽  
Author(s):  
Tatiana Duque Martins ◽  
Diéricon Sousa Cordeiro
Keyword(s):  
Emergency Situation ◽  
Daily Basis ◽  
Accurate Information ◽  
Technological Information ◽  
The World ◽  
Technological Developments ◽  
A Cell ◽  
Patent Documents ◽  
High Level ◽  
Source Of Information

Background: Face COVID-19 pandemic, a need for accurate information on SARS-CoV-2 virus is urgent and scientific reports have been published on daily basis to enable effective technologies to fight the disease progression. However, at the first moments of Pandemic, no information on the matter was known and technologies to fight the Pandemic were not readily available. However, searches in patent databases, if strategically designed, can offer quick responses to new pandemics. Objective: Aiming to provide existing information in patent documents useful to develop technologies addressing COVID-19, considering the emergency situation the world was facing and the knowledge of COVID-19 available until April, 2020, this work presents an analysis of the main characteristics of the technological information in patent documents worldwide, related to coronaviruses and the severe acute respiratory syndrome (SARS). Method: Regions of concentration of such technologies, the number of available documents and their technological fields are disclosed in three approaches: 1) a wide search, retrieving technologies on SARS or coronaviruses; 2) a targeted search, retrieving documents additionally referring to Angiotensin converting enzyme (ACE2), which is used by SARS-CoV-2 to enter a cell and 3) a punctual search, which retrieved patents disclosing aspects related to SARS-CoV-2 available at that time. Results and Conclusion: Results evidence the high-level technology involved in these developments and a monopoly tendency of such technologies, evidencing that it is possible to find answers to new problems in patent documents.

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