scholarly journals Inhibiting Arginine Methylation as a Tool to Investigate Cross-Talk with Methylation and Acetylation Post-Translational Modifications in a Glioblastoma Cell Line

Proteomes ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 44 ◽  
Author(s):  
Sabrina Samuel ◽  
Alistair Marsden ◽  
Srihari Deepak ◽  
Francisco Rivero ◽  
John Greenman ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Line ◽  
Cross Talk ◽  
3D Models ◽  
Arginine Methylation ◽  
Post Translational Modifications ◽  
Protein Arginine Methyltransferases ◽  
Average Survival ◽  
Common Grade ◽  
2D And 3D

Glioblastomas (GBM) are the most common grade 4 brain tumours; patients have very poor prognosis with an average survival of 15 months after diagnosis. Novel research lines have begun to explore aberrant protein arginine methylation (ArgMe) as a possible therapeutic target in GBM and ArgMe inhibitors are currently in clinical trials. Enzymes known as protein arginine methyltransferases (PRMT1-9) can lead to mono- or di-ArgMe, and in the latter case symmetric or asymmetric dimethylation (SDMA and ADMA, respectively). Using the most common GBM cell line, we have profiled the expression of PRMTs, used ArgMe inhibitors as tools to investigate post-translational modifications cross-talk and measured the effect of ArgMe inhibitors on cell viability. We have identified novel SDMA events upon inhibition of ADMA in GBM cells and spheroids. We have observed cross-talk between ADMA and lysine acetylation in GBM cells and platelets. Treatment of GBM cells with furamidine, a PRMT1 inhibitor, reduces cell viability in 2D and 3D models. These data provide new molecular understanding of a disease with unmet clinical needs.

Cross-talk among epigenetic modifications: lessons from histone arginine methylation

2013 ◽  
Vol 41 (3) ◽  
pp. 751-759 ◽  
Author(s):  
Diego Molina-Serrano ◽  
Vassia Schiza ◽  
Antonis Kirmizis
Keyword(s):  
Cross Talk ◽  
Influence Factor ◽  
Arginine Methylation ◽  
Epigenetic Modifications ◽  
Post Translational Modifications ◽  
Protein Arginine Methyltransferases ◽  
Chromatin States ◽  
Control Gene Expression ◽  
Functional States ◽  
Histone Arginine Methylation

Epigenetic modifications, including those occurring on DNA and on histone proteins, control gene expression by establishing and maintaining different chromatin states. In recent years, it has become apparent that epigenetic modifications do not function alone, but work together in various combinations, and cross-regulate each other in a manner that diversifies their functional states. Arginine methylation is one of the numerous PTMs (post-translational modifications) occurring on histones, catalysed by a family of PRMTs (protein arginine methyltransferases). This modification is involved in the regulation of the epigenome largely by controlling the recruitment of effector molecules to chromatin. Histone arginine methylation associates with both active and repressed chromatin states depending on the residue involved and the configuration of the deposited methyl groups. The present review focuses on the increasing number of cross-talks between histone arginine methylation and other epigenetic modifications, and describe how these cross-talks influence factor binding to regulate transcription. Furthermore, we present models of general cross-talk mechanisms that emerge from the examples of histone arginine methylation and allude to various techniques that help decipher the interplay among epigenetic modifications.

scholarly journals Betaglycan Alters NFκB-TGFβ2 Cross Talk to Reduce Survival of Human Granulosa Tumor Cells

2013 ◽  
Vol 27 (3) ◽  
pp. 466-479 ◽  
Author(s):  
Maree Bilandzic ◽  
Simon Chu ◽  
Yao Wang ◽  
Han L. Tan ◽  
Peter J. Fuller ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Survival ◽  
Cell Line ◽  
Cross Talk ◽  
Granulosa Cell Tumor ◽  
Cell Types ◽  
Nuclear Factor Κb ◽  
Chemical Inhibition ◽  
Smad3 Expression ◽  
Tgfβ Pathway

Abstract The molecular pathways controlling granulosa cell tumor (GCT) survival are poorly understood. In many cell types, nuclear factor-κB (NFκB) and TGFβ coordinately regulate cell survival to maintain tissue homeostasis. Because GCT cell lines exhibit constitutively activated NFκB, we hypothesized that NFκB blocks TGFβ-mediated cell death in GCT cells. To test this hypothesis, we used the human GCT cell line KGN, which exhibits loss of betaglycan, a TGFβ co-receptor. After inhibition of NFκB in KGN cells, re-expression of betaglycan resulted in a decrease in cell viability, which was further decreased by TGFβ2. Intriguingly, TGFβ2 increased NFκB reporter activity in control cells, but betaglycan expression suppressed both basal and TGFβ2-stimulated NFκB activity. Chemical inhibition of Mothers against decapentaplegic homolog 2/3 (SMAD2/3) signaling or SMAD2/3 gene silencing revealed that both SMADs contributed to cell survival. Furthermore, inhibiting NFκB activity resulted in a specific reduction in SMAD3 expression. Conversely, overexpression of SMAD3 increased basal NFκB activity and countered betaglycan-mediated suppression of NFκB activity. Finally, ERK1/2 activation emerged as the point of convergence of NFκB, SMAD3, and TGFβ2/betaglycan governance of GCT cell viability. Key findings in KGN cells were reproduced in a second GCT cell line, COV434. Collectively, our data establish that both SMAD2/3 and NFκB signaling pathways support GCT cell viability and suggest the existence of a positive feedback loop between NFκB and SMAD3 signaling in late-stage GCT. Furthermore, our data suggest that loss of betaglycan during tumor progression in GCT alters the functional outcomes generated by NFκB and TGFβ pathway cross talk.

scholarly journals Effect of silibinin-loaded nano-niosomal coated with trimethyl chitosan on miRNAs expression in 2D and 3D models of T47D breast cancer cell line

2017 ◽  
Vol 46 (3) ◽  
pp. 524-535 ◽  
Author(s):  
Seyede Elmira Yazdi Rouholamini ◽  
Saeid Moghassemi ◽  
Zahra Maharat ◽  
Amirhossien Hakamivala ◽  
Susan Kashanian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Cancer Cell Line ◽  
3D Models ◽  
T47d Breast Cancer Cell ◽  
Mirnas Expression ◽  
2D And 3D

scholarly journals Arginine methylation: the promise of a ‘silver bullet’ for brain tumours?

Amino Acids ◽  
2021 ◽  
Author(s):  
Sabrina F. Samuel ◽  
Antonia Barry ◽  
John Greenman ◽  
Pedro Beltran-Alvarez
Keyword(s):  
Protein Interactions ◽  
Brain Tumours ◽  
Arginine Methylation ◽  
Future Perspective ◽  
Post Translational Modifications ◽  
Protein Arginine Methyltransferases ◽  
Oncology Clinical Trials ◽  
Endogenous Modulators ◽  
Silver Bullet

AbstractDespite intense research efforts, our pharmaceutical repertoire against high-grade brain tumours has not been able to increase patient survival for a decade and life expectancy remains at less than 16 months after diagnosis, on average. Inhibitors of protein arginine methyltransferases (PRMTs) have been developed and investigated over the past 15 years and have now entered oncology clinical trials, including for brain tumours. This review collates recent advances in the understanding of the role of PRMTs and arginine methylation in brain tumours. We provide an up-to-date literature review on the mechanisms for PRMT regulation. These include endogenous modulators such as alternative splicing, miRNA, post-translational modifications and PRMT–protein interactions, and synthetic inhibitors. We discuss the relevance of PRMTs in brain tumours with a particular focus on PRMT1, -2, -5 and -8. Finally, we include a future perspective where we discuss possible routes for further research on arginine methylation and on the use of PRMT inhibitors in the context of brain tumours.

scholarly journals Techniques Used for Eye Gaze Interfaces and Survey

2015 ◽  
Vol 1 (6) ◽  
pp. 276
Author(s):  
Maria Rashid ◽  
Wardah Mehmood ◽  
Aliya Ashraf
Keyword(s):  
Eye Tracking ◽  
Eye Gaze ◽  
3D Models ◽  
Image Process ◽  
Usability Problems ◽  
Software Algorithms ◽  
Pupil Detection ◽  
Eye Movement Tracking ◽  
2D And 3D ◽  
Movement Tracking

Eye movement tracking is a method that is now-a-days used for checking the usability problems in the contexts of Human Computer Interaction (HCI). Firstly we present eye tracking technology and key elements.We tend to evaluate the behavior of the use when they are using the interace of eye gaze. Used different techniques i.e. electro-oculography, infrared oculography, video oculography, image process techniques, scrolling techniques, different models, probable approaches i.e. shape based approach, appearance based methods, 2D and 3D models based approach and different software algorithms for pupil detection etc. We have tried to compare the surveys based on their geometric properties and reportable accuracies and eventually we conclude this study by giving some prediction regarding future eye-gaze. We point out some techniques by using various eyes properties comprising nature, appearance and gesture or some combination for eye tracking and detection. Result displays eye-gaze technique is faster and better approach for selection than a mouse selection. Rate of error for all the matters determines that there have been no errors once choosing from main menus with eye mark and with mouse. But there have been a chance of errors when once choosing from sub menus in case of eye mark. So, maintain head constantly in front of eye gaze monitor.

scholarly journals Fucoxanthin Holds Potential to Become a Drug Adjuvant in Breast Cancer Treatment: Evidence from 2D and 3D Cell Cultures

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4288
Author(s):  
Fernanda Malhão ◽  
Ana Catarina Macedo ◽  
Carla Costa ◽  
Eduardo Rocha ◽  
Alice Abreu Ramos
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
3D Models ◽  
Anticancer Activities ◽  
Cytotoxic Effects ◽  
3D Cultures ◽  
3D Cell Cultures ◽  
Tumoral Cell ◽  
Microscopy Techniques ◽  
2D And 3D

Fucoxanthin (Fx) is a carotenoid derived from marine organisms that exhibits anticancer activities. However, its role as a potential drug adjuvant in breast cancer (BC) treatment is still poorly explored. Firstly, this study investigated the cytotoxic effects of Fx alone and combined with doxorubicin (Dox) and cisplatin (Cis) on a panel of 2D-cultured BC cell lines (MCF7, SKBR3 and MDA-MB-231) and one non-tumoral cell line (MCF12A). Fucoxanthin induced cytotoxicity against all the cell lines and potentiated Dox cytotoxic effects towards the SKBR3 and MDA-MB-231 cells. The combination triggering the highest cytotoxicity (Fx 10 µM + Dox 1 µM in MDA-MB-231) additionally showed significant induction of cell death and genotoxic effects, relative to control. In sequence, the same combination was tested on 3D cultures using a multi-endpoint approach involving bioactivity assays and microscopy techniques. Similar to 2D cultures, the combination of Fx and Dox showed higher cytotoxic effects on 3D cultures compared to the isolated compounds. Furthermore, this combination increased the number of apoptotic cells, decreased cell proliferation, and caused structural and ultrastructural damages on the 3D models. Overall, our findings suggest Fx has potential to become an adjuvant for Dox chemotherapy regimens in BC treatment.

Development of an Intelligent CAD System for Involute Cylindrical Gear Cutting Tools

2014 ◽  
Vol 532 ◽  
pp. 249-252
Author(s):  
Ying Hua Liao ◽  
Gao Jun Liu ◽  
Xiang Guo Sun
Keyword(s):  
Expert Knowledge ◽  
Cutting Tools ◽  
3D Models ◽  
Tool Design ◽  
Cylindrical Gear ◽  
Intelligent Cad ◽  
Forward Reasoning ◽  
Cad System ◽  
Gear Cutting ◽  
2D And 3D

An intelligent CAD system for Involute cylindrical gear cutting tools is developed by VC++ and SQL server, and it includes four modules, such as user interface, instance query, intelligent gear tool design and database. The intelligent gear tool design is the key to the intelligent CAD system, and it is based on the forward reasoning production system, and as the Intelligent reasoning technology is used for gear tool design, a lots of expert knowledge could be made full use of. The design results by the developed intelligent CAD system are more reasonable than those by a traditional CAD system, and the efficiency and quality of the gear tool design also could be improved. The developed intelligent CAD system supports both 2D and 3D models, which can lay foundation for CAD/CAE/CAM integration of gear cutting tools.

scholarly journals Extending In-Plane Impedance Measurements from 2D to 3D Cultures: Design Considerations

2021 ◽  
Vol 8 (1) ◽  
pp. 11
Author(s):  
Sorel E. De Leon ◽  
Lana Cleuren ◽  
Zay Yar Oo ◽  
Paul R. Stoddart ◽  
Sally L. McArthur
Keyword(s):  
Three Dimensional ◽  
3D Culture ◽  
Collagen Gel ◽  
Impedance Measurement ◽  
Impedance Spectrum ◽  
3D Models ◽  
Low Frequencies ◽  
3D Cell Cultures ◽  
3D Collagen ◽  
2D And 3D

Three-dimensional (3D) cell cultures have recently emerged as tools for biologically modelling the human body. As 3D models make their way into laboratories there is a need to develop characterisation techniques that are sensitive enough to monitor the cells in real time and without the need for chemical labels. Impedance spectroscopy has been shown to address both of these challenges, but there has been little research into the full impedance spectrum and how the different components of the system affect the impedance signal. Here we investigate the impedance of human fibroblast cells in 2D and 3D collagen gel cultures across a broad range of frequencies (10 Hz to 5 MHz) using a commercial well with in-plane electrodes. At low frequencies in both 2D and 3D models it was observed that protein adsorption influences the magnitude of the impedance for the cell-free samples. This effect was eliminated once cells were introduced to the systems. Cell proliferation could be monitored in 2D at intermediate frequencies (30 kHz). However, the in-plane electrodes were unable to detect any changes in the impedance at any frequency when the cells were cultured in the 3D collagen gel. The results suggest that in designing impedance measurement devices, both the nature and distribution of the cells within the 3D culture as well as the architecture of the electrodes are key variables.

scholarly journals Are STATS Arginine-methylated?

2005 ◽  
Vol 280 (23) ◽  
pp. 21700-21705 ◽  
Author(s):  
Waraporn Komyod ◽  
Uta-Maria Bauer ◽  
Peter C. Heinrich ◽  
Serge Haan ◽  
Iris Behrmann
Keyword(s):  
Arginine Methylation ◽  
Signaling Cascades ◽  
Post Translational Modification ◽  
Protein Arginine Methyltransferases ◽  
Stat Proteins ◽  
Fibrosarcoma Cells ◽  
Catalytically Active ◽  
Interferon Resistance ◽  
Stat Pathway

Transcription factors of the STAT (signal transducer and activator of transcription) family are important in signal transduction of cytokines. They are subject to post-translational modification by phosphorylation on tyrosine and serine residues. Recent evidence suggested that STATs are methylated on a conserved arginine residue within the N-terminal region. STAT arginine methylation has been described to be important for STAT function and loss of arginine methylation was discussed to be involved in interferon resistance of cancer cells. Here we provide several independent lines of evidence indicating that the issue of arginine methylation of STATs has to be reassessed. First, we show that treatment of melanoma and fibrosarcoma cells with inhibitors used to suppress methylation (N-methyl-2-deoxyadenosine, adenosine, dl-homocysteine) had profound and rapid effects on phosphorylation of STAT1 and STAT3 but also on p38 and Erk signaling cascades which are known to cross-talk with the Jak/STAT pathway. Second, we show that anti-methylarginine antibodies did not precipitate specifically STAT1 or STAT3. Third, we show that mutation of Arg31 to Lys led to destabilization of STAT1 and STAT3, implicating an important structural role of Arg31. Finally, purified catalytically active protein arginine methyltransferases (PRMT1, -2, -3, -4, and -6) did not methylate STAT proteins, and cotransfection with PRMT1 did not affect STAT1-controlled reporter gene activity. Taken together, our data suggest the absence of arginine methylation of STAT1 and STAT3.

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